EFFECT OF WHOLE GRAIN BREAKFAST CEREAL ON SATIETY AND SHORT-TERM FOOD INTAKE. ; Nestlé Research Centre, Nestec Ltd P.O. Box 44
An association between whole grain (WG) intake and lower risk of obesity is well documented. We investigated whether this may, at least partly, be mediated through appetite by comparing WG breakfast cereal (94.5% WG) against refined cereal (0% WG) with respect to their effects on satiety and short-term food intake. We studied unrestricted healthy men and women after an overnight fast in a single-blind randomized crossover design. Forty-five grams of cereal was served with 125 ml of milk (2.7% fat) and 250 ml water. Subjective feelings of satiety, thirst and palatability were measured using validated visual analogue scales at 15-min intervals before and after eating. Ad libitum food intake was measured 2 hrs later. Satiety was assessed with a composite score for satiety (CSS), averaging fullness and the inverse of hunger, desire-to-eat and prospective consumption.
Research was funded by Nestec SA and Cereal Partners Worldwide
ORAL INTAKE AND POST-ORAL REINFORCEMENT BY CORN OIL AND ENOVA OIL IN RATS. . ; Brooklyn College of CUNY
Enova oil is a blend of vegetable oils processed to contain a high concentration of 1,3 diglycerides (DG). It is marketed as an alternative to standard triglyceride (TG) oils, because it is oxidized rather than stored as body fat. Rodent studies have found no differences in intake of high-fat mixed diets made with DG or TG oil. We examined whether rats would respond differently to DG and TG oil emulsions presented as separate sources of food, and whether the oils differed in reinforcing flavor preferences. In Experiment 1, food-restricted rats were trained in 30-min sessions with CS flavors paired with IG infusions of 7.1% corn oil (TG) and Enova oil (DG) emulsions to compare their reinforcement potency. Both oil-paired flavors were preferred (71-72%) to a water-paired flavor, and rats consumed the two oil-paired flavors equally in a choice test between them. 1- and 2-bottle oral intakes of the emulsions were also similar. The emulsions were equally satiating when infused as rats drank a palatable low-energy fluid. In Experiment 2, ad libitum-fed rats consumed similar amounts of DG and TG emulsion in 1- and 2-bottle tests (2 days each). On 1-bottle days, chow intake was lower with DG than with TG, suggesting that DG-fed animals might maintain lower energy intakes. Other rats were given 7.1% DG or TG and chow for several weeks. DG-fed rats consumed only half as much oil emulsion as TG-fed rats, and the TG group consumed more total energy and gained more weight than chow-only controls. DG oil thus appears to be equally acceptable and equally reinforcing, but leads to less overeating than TG oil.
Supported by NIH DK31135
COFFEE INTAKE, FEEDING BEHAVIOR AND ACTIVITY IN RATS . ; Feeding Behavior and Nutrition Research Center, CUSur, University of Guadalajara
The experimental evidence demonstrates that an important relation between activity and feeding behavior exists. The objective of this experiment was to evaluate the effects of coffee consumption on feeding behavior and patterns of activity in albino rats. Eight rats, 4 males and 4 females of three months of age were assigned randomly to 2 experimental groups. The experiment was divided in 5 phases. In phases 1, 3 and 5, all subjects were exposed to 200ml of water during half an hour, followed of half an hour of access at activity wheel and when finalizing were exposed to 2 hrs of free access. In 2 and 4 phases, group 1 was exposed to a solution of 1g of coffee and 7.5g of sugar and group 2 to a solution of 7.5g of sugar during the half hour of access to the water. Results showed that water consumption with sugar was greater consumption in comparison with coffee in the females. Coffee and sugar consumption was greater in comparison with the sugar consumptions In males. The subjects exposed to coffee solution registered a greater activity. Subjects exposed to the sugar solution diminished their activity
LEPTIN MODULATES OLFACTORY ACUITY. ; 1Obesity Research Center, GRI, 2UMR5020 Neurosciences Sensorielles Comportement Cognition
We have previously shown that olfactory acuity is modulated by nutritional status. This suggests that olfactory function is under the control of neuroendocrine signals that modulate feeding behavior. Although the anorectic hormone leptin is well known to regulate food intake and energy expenditure, its action on olfactory function is postulated by the presence of its receptor in the olfactory bulb (OB). In this study, we have performed histological, electrophysiological and behavioral experiments in order to determine whether leptin is implicated in the modulation of olfactory function. Firstly, we have demonstrated that the long isoform of the leptin receptor is highly expressed in the OB and is mostly localized in mitral cells (main neurons) and granular cells. Furthermore, patch-clamp experiments show that leptin modulates mitral cells spontaneous activity either through an increase or a decrease in their mean firing frequency. In addition, using a behavioral test designed to measure sensitivity to odorants, we found that CNS delivery of leptin decreases olfactory sensitivity in a dose-dependent manner. By contrast, obese Zucker fa/fa rats, carrying a non functional leptin receptor, display higher olfactory sensitivity than their lean controls. Taken together these data suggest that leptin is able to modulate olfactory sensitivity by altering the transmission of the sensory stimulus in the OB. These results support the notion that the sense of smell participates in the regulation of ingestive behavior by responding to hormonal cues of nutritional status.
HIGH CALCIUM PREFERENCE IS ASSOCIATED WITH LOW EXPRESSION OF THE CALCIUM-SENSING RECEPTOR GENE, CASR, IN TONGUE EPITHELIAL TISSUE . ; Monell Chemical Senses Center
Calcium is essential for survival but high concentrations of calcium are unpalatable to humans and most animals avoid them. An exception is the PWK/PhJ (PWK) strain of mice, which in contrast to the C57BL/6J (B6) and other inbred strains, avidly and specifically ingests calcium. A genome scan of B6 x PWK F2 hybrid mice linked a component of this strain difference to a region on chromosome 16 at microsatellite marker D16Mit60 (32.6 Mb, 23.4 cM), with a peak LOD score of 8.0. Nearby (36.4Mb, 26.3 cM) is the calcium-sensing receptor gene, Casr, which has a central role in extracellular calcium homeostasis. To evaluate Casr as a candidate gene responsible for the behavioral phenotype, we compared Casr DNA sequences between B6 and PWK mice. There were six polymorphisms in the coding region but these were synonymous and so were unlikely to influence receptor function. However there were several polymorphisms upstream, which may affect the amount of mRNA expressed. Therefore, we measured expression of Casr mRNA in B6 and PWK mouse taste and non-taste tissues by real-time quantitative PCR. Using three Casr gene expression assays with probes targeting different parts of the gene, we found that Casr expression was 1.5 – 7.0 fold higher in B6 than PWK in both taste and non-taste epithelial tissues. We speculate that Casr expression negatively regulates calcium intake, so the PWK strain’s avidity for calcium is due, at least in part, to relatively low expression of Casr in taste or other tissues.
WITHIN-MEAL EATING RATE AND 1-HOUR APPETITE IN SLOW, MEDIUM, AND FAST PACED EATERS. ; University of Rhode Island
Eating slowly is recommended for weight management, but data are lacking on how it may influence energy intake regulation, and if it can be easily adopted. We asked 90 females (22±6yr; BMI=22±3) to rate themselves as slow (n=13), medium (n=47), or fast (n=30) eaters. During the mid-follicular phase, after a standardized breakfast and 4 hour fast, they ate an identical ad libitum pasta lunch on two occasions, once instructed to eat quickly and once slowly. They completed visual analogue scales of hunger (H), satiety (S), and desire-to-eat (DTE) before and 60 minutes after lunch. Eating rate (61±43Kcal/min) correlated positively with 60-minute H (r=0.207, p=0.005) and DTE (r=0.244, p=0.001), and negatively with S (r=-0.151, p=0.044). Meal duration was not correlated with energy intake, but it was negatively correlated with DTE at 60 minutes (r=-0.171, p=0.022). At 60 minutes, H (9±12 vs. 13±13; p=0.00122) and DTE (10±12 vs. 16±14; p=0.00003) were lower (r=0.00122, p=0.00002) and S higher (84±16 vs. 77±20; p=0.00021) after slow versus quick eating. Slow eaters ate less (626±220kcal) than medium paced eaters (724±169kcal; p=0.036). Whether told to eat quickly or slowly, slow eaters tended to eat slower (54±42Kcal/min) than medium (60±41Kcal/min) or fast eaters (66±47Kcal/min; p>.05). These findings suggest that eating rate may be important in 60 minute H, S, and DTE, slow eating may be uncommon in young women, and one-time instruction on changing habitual eating rate may not be effective enough.
EFFECTS OF IRREGULARITY AND PREDICTABILITY OF THE TIME OF DAILY SESSIONS ON RATS' FEEDING BEHAVIOR . ; Doshisha University
This study tested the effects of irregularity and predictability of time of daily sessions on rats’ feeding behavior. Daily 1.5 hour feeding was provided in the homecages. In a regular group (N=6), daily 1.5-hour feeding was provided at 10:00AM. In an irregular group (N=6), daily sessions started at 1 of 2 different times (10:00AM or 5:00PM) with average inter-session interval of 22.5 hours. In a signaled group (N=6), the time of the session was yoked to the irregular group but a signal (an empty food tray in the homecage) was provided 30 min prior to the sessions. No supplemental food was provided. The experiment lasted for 12 days. Daily food consumption increased in the regular group but not in the irregular group. Daily food consumption in the signaled group was similar to that in the regular group. Rats in the irregular lost more body weight than rats in the regular and signaled group. These results suggest that unpredictability of the feeding schedule is responsible for the deteriorating effects of irregular feeding schedule.
SEROTONIN 2C RECEPTOR (5HT2CR) SIGNALING IS NECESSARY FOR, AND DISSOCIATES THE NEURAL PATHWAYS OF, THE SATIATING EFFECTS OF CHOLECYSTOKININ (CCK ) AND GLUCAGON-LIKE PEPTIDE-1 (GLP-1). ; Institute of Animal Science ETH-Zurich
To investigate the role of 5HT2CR in the satiating actions of gut peptides, we examined (1) the effect of null mutations (KO) of 5HT2CR on the feeding-inhibitory potencies of CCK (1, 2, or 4 μg/kg, IP) and GLP-1 (100, 200 and 400 nmol/kg, IP) and (2) their effects on the distribution of c-Fos immunoreactivity (cFIR) in the brain. The feeding-inhibitory effect of leptin (1 mg/kg, SC) was tested as a positive control (Nonogaki et al., 1998). Peptides were injected at dark onset. Food intake was measured 30 min and 1, 2 and 4 h later. As expected, leptin decreased food intake similarly in both genotypes. cFIR was measured 90 min after dark onset in unfed subjects. All CCK and GLP-1 doses decreased food intake in WT, but not KO mice. CCK (2 µg/kg) induced cFIR in the NTS of WT, but not KO mice, whereas it induced cFIR similarly in the PVN and Arc of both genotypes. GLP-1 (100 nmol/kg), on the other hand, increased cFIR expression similarly in the NTS of both genotypes, but increased cFIR expression in the PVN and Arc of KO, but not WT mice. These results support the hypothesis that 5HT-5HT2CR signaling is necessary for the full satiating effects of CCK and GLP-1, but suggest that the satiating effects are mediated by different mechanisms. Further, the data dissociate the sites and neural mechanisms (i.e., increased vs. decreased cFIR activation) of CCK and GLP-1-induced satiation.
TEST TITLE . ; asdfadsf
BENZODIAZEPINE MODULATION OF GUSTATORY CODING IN THE PARABRACHIAL NUCLEUS. . ; Psychology & Neuroscience, Amherst College
Benzodiazepine agonists delivered systemically or to the parabrachial nucleus (PBN) increase consumption and behavioral measures of gustatory evaluation. However, electrophysiological PBN gustatory responses after benzodiazepines have not been characterized. We evaluated PBN gustatory neuron responses before and after injections of chlordiazepoxide (CDP). Gustatory responsive cells in the PBN were profiled for responses to 1.0M sucrose, 0.1M NaCl, 0.03M citric acid, and 0.003M QHCl before and/or after systemic CDP (20 mg/kg) or saline delivery. Of the 129 cells recorded, 16 cells were tested both before and after CDP injection and 7 cells were tested both before and after saline. In this CDP subgroup, spontaneous activity and the responses to QHCl were significantly suppressed. Responses to sucrose, NaCl and citric acid were not changed, however, more cells responded best to sucrose and fewer responded best to citric acid and QHCl after CDP. Breadth of tuning (entropy) was reduced after CDP in cells that were broadly tuned initially. No such changes occurred after saline injection. In the “between” groups, after CDP the magnitude of responses to citric acid and QHCl were reduced. The proportion of cells responding best to sucrose also more than doubled. There were no shifts after saline injection. Overall, CDP reduced the response magnitude and/or proportion of cells responding best to citric acid and QHCl, and it increased the proportion of cells responding best to sucrose. Thus, CDP may modify taste evaluation through taste quality-specific rate-coding effects in the PBN. [Supported by NIH DC-007389]
OREXIN-A HYPERPHAGIA: BEHAVIORAL MICROSTRUCTURE AND THE ROLE OF THE AREA POSTREMA. . ; Psychology and Neuroscience, Amherst College
Orexin-A (ORA) is an orexigenic neuropeptide produced in perikarya limited to the lateral hypothalamus. The motivational and anatomical bases of ORA hyperphagia remain unclear. We used lick microstructure analysis to evaluate hindbrain and forebrain ORA effects in intact and hindbrain-lesioned rats. Intact rats with cannulas in the 4th ventricle received vehicle (2 μl aCSF) or ORA (0.1, 0.4, 1 or 10 nM/ 2μl) injections 15 min prior to 90 min access to 0.1M sucrose. The most effective dose (1 nM), which doubled intake, was then applied in 4V cannula-fitted rats tested for licking of water, 0.1M and 1.0M sucrose solutions, to vary caloric and gustatory intensity. ORA increased intake for 0.1M sucrose only, by prolonging the meal without affecting early ingestion rate or burst size, suggesting that hindbrain ORA affected inhibitory post-ingestive feedback rather than taste evaluation. Next, rats with cannulas in the 3rd ventricle received area postrema lesions or sham procedures prior to 1 nM ORA ingestion tests for water, 0.1M and 1.0M sucrose. ORA effects in the sham group replicated those after 4V injection, and the meal size increase was nearly identical between 3V and 4V ORA groups. Hyperphagic responses to 3V ORA were abolished in the APX group, although the taste solutions still produced reliable differences in licking measures of postingestive feedback inhibition and taste evaluation under control conditions. The results emphasize a role for ORA in the area postrema and the nucleus of the solitary tract in feeding control. [Amherst College, HHMI & NIH DC-07382]
CFOS-LI IN MALE AND FEMALE RAT BRAIN FOLLOWING ADMINISTRATION OF MERCAPTOACETATE. . ; Purdue University
Administration of lipoprivic drugs, such as mercaptoacetate (MA), has been demonstrated to stimulate food intake in male rats, and previous work using cFos immunohistochemistry has implicated the nucleus of the solitary tract (NTS), the central subnucleus of the lateral parabrachial nucleus (lPBN), the central nucleus of the amygdala (CNA, lateral part), and the dorsal motor nucleus of the vagus (DMV) as neural substrates that may underlie the increased ingestive behavior. In female rats, MA does not stimulate food intake, but does interfere with reproductive behavior and physiology, for example, by suppressing GnRH and LH release. The present experiment was designed to examine neural substrates that might contribute to the differential behavioral responses of male and female rats to administration of MA by examining patterns of cFos-li. Adult male and female rats were injected with 69 mg/kg MA or 0.15 M NaCl i.p. Two hours later, animals were perfused transcardially, brains removed and 40 micron coronal sections were collected. The brains were processed for c-Fos immunohistochemistry. Cells labeled with cFos were counted in the NTS, the CNA, the lPBN, the ventral hypothalamic nucleus (VLH), the paraventricular hypothalamus (anterior parvicellular) (PaAP), the arcuate hypothalamic nucleus (Arc), the dorsomedial hypothalamic nucleus (DMH), the medial preoptic nucleus (MPO), and the area postrema (AP).
PEPTIDE YY: FOOD FOR THOUGHT. ; University College London
Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour. In response to eating, several hormones are released from the gut which play a role in regulating body weight. Peptide YY (PYY), circulating predominantly as an N-terminally truncated form PYY3–36, is one such hormone. Exogenous administration of PYY3-36 reduces food intake in obese humans and rodents. Moreover, new lines of evidence support a role for endogenous PYY3-36 in body weight regulation. The NPY-Y2 receptor mediates the anorectic actions of PYY3-36 with rodent studies implicating the hypothalamus, vagus and brainstem as key target sites. To investigate in humans the brain circuits upon which PYY3–36 acts a double-blind placebo controlled study was undertaken, combining PYY3–36 infusion, continuous functional magnetic resonance imaging and behavioural measures. PYY3–36 modulated neural activity within brainstem and hypothalamic regions consistent with rodent studies. However, the greatest effect of PYY3–36 on brain activity was seen within the left caudolateral orbital frontal cortex (OFC), a polymodal brain region implicated in reward processing. Under high PYY3–36 plasma conditions, mimicking the fed state, changes in neural activity within the OFC predicted subsequent feeding behaviour. In contrast, in low PYY3–36 conditions, hypothalamic activation predicted subsequent food intake. Thus the presence of postprandial plasma concentrations of PYY3–36 switched food intake regulation from a homeostatic to a hedonic, corticolimbic area.
EATING FOR PLEASURE OR CALORIES: NEURAL INTEGRATION OF COGNITIVE, EMOTIONAL, AND METABOLIC DRIVES. ; Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, LSU System
Exposed to palatable and energy dense foods and a sedentary lifestyle, predisposed humans and rodents develop obesity despite homeostatic regulatory mechanisms. An evolutionarily conserved system rigorously defending the lower, but only weakly the upper limits of adiposity appears to be the underlying principle. Powerful hormonal and neural signaling mechanisms have evolved to broadcast nutrient deficiency throughout the body orchestrating optimal responding by preserving existing and procuring new energy sources. Examples include ghrelin secreted from the empty gut and low leptin levels from inadequate fat stores. Both, ghrelin and low leptin stimulate the food-finding processes through their actions on brain systems involved in sensory perception, spatial exploration, learning and memory, reward, and ingestion. While highly responsive to nutrient depletion signals, these functions are relatively resistant to signals reflecting normal or increased levels of adiposity. As a consequence, the “normal“ level of activity in cortico-limbic systems of reward responds to the rich food environment to produce hyperphagia and obesity in prone individuals. This conclusion is supported by genetic analyses in humans, showing that most of the predisposing genes primarily affect food intake. The three most promising options to prevent or treat hyperphagia and obesity currently are 1) changes in the food environment, 2) pharmacological tools tweaking critical brain systems, or 3) surgical interventions. DK47348, DK 071082.
DORSOMEDIAL HYPOTHALAMIC NEUROPEPTIDE Y MODULATES THE SATIETY ACTIONS OF PERIPHERAL CHOLECYCTOKININ. ; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine
Previous studies have suggested that dorsomedial hypothalamic (DMH) neuropeptide Y (NPY) may serve as an important signal to regulate energy balance. In this study, we sought to assess a role for DMH NPY in feeding control using adeno-associated virus (AAV)-mediated RNAi (AAVshNPY) for knocking down NPY gene expression in the DMH. We injected AAVshNPY bilaterally into the DMH and examined the feeding effects of knockdown of DMH NPY gene expression in Sprague-Dawley rats. We found that although body weight gain and daily food intake were not significantly affected by AAVshNPY, AAVshNPY rats had altered meal patterns. Meal size was significantly decreased primarily during the dark cycle in AAVshNPY rats. In compensation for this decrease, meal number was increased. We further found that knockdown of DMH NPY gene expression enhanced the feeding response to peripheral administration of cholecyctokinin (CCK). Peripheral CCK administration produced a greater feeding inhibition in AAVshNPY rats relative to rats receiving control vectors (AAVshCTL). Consistent with this feeding effect, c-Fos like immunohistochemistry revealed that peripheral CCK administration increased the number of c-Fos positive cells in the nucleus of the solitary tract at a greater level in AAVshNPY rats as compared with AAVshCTL rats. Together, these results suggest that DMH NPY plays an important role in modulating within meal satiety signaling. (Supported by NIH DK074269)
THE EFFECT OF ALCOHOL-PAIRED CONTEXTUAL CUES ON RESPONSES TO A NOVEL ALCOHOLIC DRINK . ; School of Psychology, University of Birmingham
The study tested whether the repeated pairing of contextual cues with the unconditioned effects of an alcoholic drink results in such cues eliciting conditioned compensatory responses to the disinhibitory effects of alcohol. Sixteen social drinkers (mean age 20.1 yrs, male n =8) alternated over days between consuming a non-alcoholic placebo drink in one context, and consuming the same drink containing vodka at doses of 0.65 g/kg body weight for males and 0.57 g/kg for females, in a different context. Half of the participants received alcohol in one context, and the other half placebo in that context. Also, half received alcohol first, and the other half placebo first. At baseline and 8 minutes post-consumption, participants completed computer-based tests of response inhibition. The procedure was repeated over six separate conditioning sessions (3 placebo and 3 alcohol sessions). On the subsequent session (test for a conditioned response), participants received alcohol in a novel drink in either their alcohol-paired context or in their placebo-paired context. Alcohol increased the number of false alarms committed on an affective go/no-go task, and tolerance was shown to this effect over conditioning sessions. At test, participants who received the novel alcoholic drink in their alcohol-paired context committed fewer false alarms than did participants who received the same drink but in their placebo paired context. These data suggest that contexts associated with the consumption of alcohol can condition compensatory responses to the dishinibitory effects of alcohol.
THE GREATER SUPERFICIAL PETROSAL NERVE IS UNNECESSARY FOR NORMAL RESPONSIVENESS TO SUCROSE BY RATS IN A BRIEF-ACCESS TEST, REGARDLESS OF TRIAL LENGTH.. ; Dept. of Psychology & Program in Neuroscience, Florida State University
Of all the gustatory nerves in rats, the greater superficial petrosal nerve (GSP) is the most sensitive to sugars placed on its palatal taste receptors, but the literature is mixed concerning its importance in behavioral responsiveness to sugar. In a recent study from our laboratory, transection of the GSP (GSPx) did not affect concentration-dependent licking to sucrose in a brief-access test, but total trials (5-s) taken decreased, suggesting that the absence of input may have selectively affected appetitive behavior but spared consummatory responses. Here, rats were tested before and after bilateral GSPx or sham surgery (n=8/group) in 30-min brief-access tests with 6 concentrations of sucrose quasi-randomly delivered for either 5-s or 30-s trials to determine the effect of trial length. There was no difference between surgical groups in either licks/concentration or total number of trials taken. Histological confirmation of the transection is in progress. In sum, the GSP appears unnecessary for maintaining the affective response to sucrose as measured here, but it might be important for other behaviors related to taste quality identification. The fact that combined GSP and chorda tympani transection has been shown to markedly reduce sucrose licking in a brief-access test while individual nerve cuts have little effect supports the view that affective taste processing involves convergent peripheral input from disparate taste receptor fields. Supported by R01-DC01628.
NINTENDO WII VS. MICROSOFT X-BOX: DIFFERENTIAL EFFECTS ON MOOD, PHYSIOLOGY, SNACKING BEHAVIOR, AND CALORIC BURN. ; Wheeling Jesuit University
Prior research has investigated the link comparing childhood obesity with activity participation, television viewing, and video game use. The current study used 27 participants to compare performance, mood, cognition, physiological measures, and snacking behavior between the Nintendo Wii and the Microsoft Xbox gaming systems. Each participant played a boxing game on both the Wii and the Xbox, and also completed a control condition where no game was played. During play, participants wore an Actiwatch monitor, which measured their movement and caloric expenditure. The results showed that there was a significantly higher blood pressure and pulse with the Wii than with either the Xbox or control conditions. The results also showed mental demand, physical demand, and self-evaluated performance were highest in the Wii condition. Furthermore, there were greater total and mean activity scores in the Wii condition which led to a greater calorie expenditure. Finally, when a snack food (M&Ms) was available during game play, those participants in the Wii condition ate the least amount of the snack. These results are particularly salient regarding the positive benefits of video game play.
MEDIOBASAL HYPOTHALAMIC LEUCINE METABOLISM INHIBITS FOOD INTAKE AND LEUCINE ACTIVATES POMC AND LEPR NEURONS . ; Albert Einstein College of Medicine
In response to nutrient stimuli, the mediobasal hypothalamus (MBH) engages multiple neuroendocrine mechanisms to regulate behavioral and metabolic determinants of energy balance. Recent data indicate that brain leucine sensing contributes to the regulation of food intake and body weight but the neurobiological substrates and physiological effectors mediating central leucine's actions are unknown. Consequently, we characterized the effects of MBH leucine in male C57/Bl6 mice. MBH leucine injection (206 pmol in 100nl) induced a significant 20% reduction in 24h food intake, decreased 24h body weight change but did not affect oxygen consumption, respiratory quotient, physical activity or core temperature compared to aCSF vehicle injections. The decrease in food intake was due to both a 50% reduction in first meal size and a sustained decrease in meal number beginning 8h after injection. Acute MBH injection of α-ketoisocaproic acid, the product of leucine transamination, recapitulated the effects of MBH leucine injections. Chronic MBH activation of branched-chain amino acid decarboxylation via minipump delivery of α-chloroisocaproic acid also decreased food intake, solely by reducing meal size, and reduced body weight gain. MBH leucine injection in POMC-GFP and LepR-GFP mice increased c-fos immunoreactivity in arcuate POMC and LepR neurons, and leucine depolarized POMC-GFP neurons in perfused arcuate slices. Taken together, these data suggest that MBH leucine metabolism inhibits food intake by activating POMC and LepR neurons.
PERSONALITY AS A RISK FACTOR FOR ADIPOSITY AND INSULIN RESISTANCE. ; Department of Neuroendocrinology, University of Groningen
The personality of an individual may be an important risk factor for the development of weight gain and insulin resistance. We study this and we particularly focus on differences between so-called active and passive personalities, selected from special rat strains that display a large variety of behavior.
We found that passive rats eat a few large meals at a low speed. Active rats eat more frequent and faster but take smaller meals. Active rats take almost all their meals in the dark period, passive individuals are taking relatively more meals in the light phase. Total daily intake is not different between the two personalities. Indirect calorimetry revealed that passive rats have a lower resting energy expenditure and carcass analysis showed that passive rats have a higher percentage of fat in the visceral compartment. When given a palatable medium fat diet, both personalities increase daily food intake. This increase is larger in passive rats, making them more susceptible for diet-induced obesity.
Passive individuals are also more susceptible for developing insulin resistance. We found in a series of intravenous glucose tolerance tests that both baseline insulin levels and insulin responses are markedly increased in passive individuals, an effect that is independent of the diet.
We conclude that passive individuals are more prone to develop adiposity and insulin resistance. However, we also found that, when given the opportunity to become physically active, passive individuals will increase their daily activity, a phenomenon that does not occur in so-called active rats.
TASTE OF SAVOURY FOODS DOES NOT NEED A FIFTH RECEPTOR TYPE. ; School of Psychology, University of Birmingham
‘Savoury’ is a culinary concept used in the UK to complement the construct of ‘a sweet’ in the sense of a dessert. Hence foods in main courses or appetisers are also savoury if they are not sweet. At a conference in 1993 sponsored by the Japanese brewer of monosodium glutamate (MSG), it was claimed that the term ‘umami’ is equivalent to ‘savoury’ in naming a balance of bitter, sweet, sour and salty tastes that is in common among meat and vegetables because monohydrogen glutamate and sodium are the most abundant ions in tissues of such species. Hence it was suggested that there need not be a human taste receptor for MSG or amino acids in general. This thesis was decried on the fallacious grounds that multidimensional scaling distinguishes the taste of MSG from that of the four classic tastes. Nevertheless the British term ‘savoury’ has since become widely used for the taste of glutamate and the class of dishes formerly called ‘salty.’ When cognitive interactions among signals from NaCl, citric acid, caffeine, sucrose and MSG when characterising a food such as tomato juice or chicken soup are measured properly by multiple discrimination scaling, the top-quality mixture of tastants is matched best by summation of distances of two or three of the four basic tastes from their learnt norm. Therefore an amino acid taste receptor on the human tongue need play no major role in the overall taste of a savoury food. Indeed, that receptor may merely be another mutation of bitter receptors that retains sensitivity to amide nitrogen while gaining the sensitivity to hydroxyl oxygen of a sweet receptor.
GHRELIN/LEPTIN RATIO TRACKS ENERGY BALANCE, WHILE RATINGS OF APPETITE TRACK ONLY MEAL SIZE AND GIVE PARADOXICAL VALUES TO EXERCISE ENERGY EXPENDITURE. . ; 1Division of Kinesiology, The University of Michigan, 2Department of Internal Medicine, the University of Michigan
Ghrelin and leptin are, respectively, putative hunger and satiety hormones, so that their ratio (Ghr/Lep) has been identified as a hunger signal (Ann Intern Med 2004,141:846-850). We tested the hunger-signal hypothesis by comparing ratings of hunger and satiation to Ghr/Lep under three conditions of positive energy balance (EB) and two conditions of negative EB in 12 healthy female volunteers. A 500 Kcal meal at 6 h in a sedentary trial served as a positive EB control. To produce negative EB, 400 Kcal were either withhheld from breakfast or expended through 2 h of exercise. EB was restored with a 400 Kcal intravenous nutrient infusion. Ghrelin and leptin concentrations were measured throughout. Negative EB was associated with increased Ghr/Lep and positive EB withreduced Ghr/Lep. Only dietary restriction increased hunger and decreased satiation. During exercise regardless of the state of EB, hunger was suppressed and satiation ratings increased. We conclude that Ghr/Lep appropriately tracks EB but does not influence ratings of hunger and satiation. Hunger and satiation appropriately reflect changes in meal size but are unresponsive to changes in EB caused by exercise or intravenous nutrient replacement. During exercise, and unrelated to prevailing EB, hunger ratings are paradoxically decreased and satiation increased.
Support: NIDDK 1R15DK066286-01A2 and Tanita Healthy Weight Community Trust grants.
DOES TODDLERS&RSQUO; FOOD INTAKE DIFFER ACCORDING TO VARIATIONS IN FAT, SALT OR SUGAR IN FOODS?. ; INRA, UMR 1129 FLAVIC
In many developed countries, governmental policies encourage reduction of fat, salt and sugar consumption. However, such reductions are likely to impact the palatability of foods, in particular in children, whose food intake is largely influenced by food’s sensory features. The extent to which young children’s food intake varies according to fat, salt and sugar content is imperfectly known.
This study aimed to evaluate whether toddler’s food intake varied from one meal to the other (1) during lunches where salt or fat contents were modified in some foods and (2) during snacks where sugar or fat contents were modified.
Sixty-four children (24-36 months old) participated in the study in their usual daycares. Children participated in 10 lunches composed of the same menu (vegetable salad, chicken, green beans, pasta, and yogurt) every other week. Across lunches, we varied the salt content (0, 0.6 and 1.2g/100g) or the fat content (0, 2 and 4 g/100g) in green beans or in pasta. Children participated in 18 snacks, composed either of soft white cheese varying in fat content (0, 20, 40%) or of apple-peach purée varying in added sugar content (0, 5, 10 g/100g) ; the three variants of cheese and of purée were offered three times each. During each lunch or each snack, children were set free to eat as much as they wanted. Intake of each food was quantified by weighting the food before and after the meal.
The study is currently ongoing. Results will be discussed in terms of varied palatability according to fat, salt and sugar level, and of children’s habits of discretionary use of fat, salt and sugar.
GASTRIC EMPTYING IS SLOWER, AND HUNGER AND ENERGY INTAKE ARE LESS, PRE-OVULATION WHEN COMPARED WITH POST-OVULATION IN HEALTHY WOMEN. ; 1University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, 2Institute of Medicine, Division of Gastoenterology, Haukeland University Hospital, University of Bergen
BACKGROUND: There is evidence that the menstrual cycle affects appetite, such that energy intake is lower pre-ovulation than post-ovulation. Since changes in gastric emptying (GE) contribute to acute energy intake, an understanding of how the menstrual cycle affects GE is important. Moreover, knowledge on day-to-day variations in energy intake, ie within the same phase of the menstrual cycle, is limited. AIMS: To assess the hypotheses that (i) GE is slower, and hunger and energy intake are less, pre-ovulation than post-ovulation, (ii) GE and energy intake are reproducible when assessed twice within a particular phase of the menstrual cycle (eg pre-ovulation) and (iii) the reduction in hunger and energy intake pre-ovulation will be related to slower GE. METHODS: 9 healthy, lean females (aged 32±1 years; BMI: 21.6±0.5 kg/m²) were studied on 3 separate occasions; twice pre-ovulation (between days 6-12), and once post-ovulation (between days 18-24). Visits were randomized in single-blind fashion over consecutive menstrual cycles. Following consumption of a 300 ml glucose drink (815 kJ), GE (using 3D ultrasound) and hunger (using visual analogue scales) were measured for 90 min. Between 90-120 min, energy intake at a buffet meal was quantified. RESULTS: During pre-ovulation, GE was slower (P<0.05), while hunger (P<0.01) and energy intake (P<0.05) were less, when compared with post-ovulation. There were no differences in any of the parameters between the two pre-ovulation visits. There were inverse relationships between both scores for hunger immediately before the buffet meal and energy intake with GE (AUC) (r= -0.5, P<0.05 for both). CONCLUSION: Hunger and energy intake are lower pre-ovulation and associated with slower GE when compared with post-ovulation. Furthermore, there are no differences between these parameters when assessed twice during pre-ovulation. Taken together, the phase of the menstrual cycle should be controlled for when evaluating gastrointestinal function and energy intake in female volunteers.
CENTRAL ADMINISTRATION OF AN NF&KAPPA;B ANTAGONIST PRIOR TO INSULIN REDUCES FOOD INTAKE AND BODY WEIGHT IN RATS ON A HIGH-FAT DIET.. ; 1Department of Nutrition, University of North Carolina at Greensboro, 2University of Texas Southwestern Medical Center, Department of Internal Medicine, 3Obesity Research Center, University of Cincinnati, Department of Psychiatry
Ingestion of a high-fat (HF) diet leads to hypothalamic leptin and insulin resistance. It is increasingly recognized that obesity is characterized by chronic activation of inflammatory pathways and that inflammatory signaling pathways in obesity are causally linked to insulin resistance. SN50 is an NFκB antagonist that binds to NFκB in the cytoplasm to block it from entering the nucleus. In the present studies we compared the effects of central insulin and SN50 in rats maintained on either a HF or a matched low-fat (LF) diet. After the rats were on the HF diet for a month they were given double intra-3rd-ventricular (i3vt) injections of saline, 10 mU insulin or 2 µg SN50 in a Latin square design. Saline/saline double injections and SN50/saline injections were not anorectic and did not reduce body weight. As expected rats on the HF diet were insulin resistant, so there was no decrease in food intake or body weight in the saline/insulin paradigm. In contrast, rats given SN50 prior to insulin reduced their food intake and body weight. Hence, blocking NFκB with SN50 was efficacious at reducing food intake in insulin-resistant animals on a HF diet. These data suggest that decreasing central inflammation restores insulin sensitivity and this may lead to approaches to circumvent insulin resistance.
HYPOTHALAMIC INTEGRATION OF HORMONAL INPUTS . ; Institute for Genetics, University of Cologne
Neuropeptide Y (NPY) - and agouti-related peptide (AgRP) - as well as proopiomelanocortin
(POMC)-expressing neurons in the arcuate nucleus of the hypothalamus integrate multiple hormonal and nutrient signals to adapt energy homeostasis and peripheral glucose metabolism. The presentation will focus on the common intracellular signaling pathways activated by these signals in defined neurons of the arcuate nucleus of the hypothalamus such as the activation of the Pi3 kinase and STAT3 signaling pathway. Data from transgenic mice with either deletions or constitutive activations of these pathways in AgRP and POMC neurons will be presented. The functional consequences of modulating these unifying intracellular pathways and their regulation by diverse upstream activators will be discussed.
THE ROLE OF LEARNING IN EXPECTED SATIETY AND DECISIONS ABOUT PORTION SIZE.. ; University of Bristol
In humans, meal size is often determined before a meal begins, i.e., we typically eat what we place or find on our plate. Given the importance of portion size as a determinant of energy intake, it is surprising that scant attention has been paid to the basis on which portion-size decisions are made. To explore this issue a ‘method of constant stimuli’ can be used to quantify and compare a person’s beliefs about the satiety that different foods are expected to deliver (calorie for calorie). This psychometric approach reveals that ‘expected satiety’ differs considerably across foods. One reason for this is that expected satiety is learned over time. Several findings are reviewed that support this claim. For example, across a range of foods, participants expect familiar foods to confer greater satiety and they express greater confidence in these expectations relative to unfamiliar foods. Expected satiety is also influenced by the context in which a food has been encountered in the past. In particular, foods tend to have higher expected satiety if they have previously produced feelings of fullness. Finally, and perhaps the best evidence for learning, expected satiety can be manipulated directly. This form of conditioning is demonstrated by measuring a change in expected satiety before and one day after consuming a novel high- or low-energy dense test food. Together, these findings are of interest, because they illustrate a new kind of dietary learning. This form of learning is potentially very important, because it may help to explain why certain foods are selected and subsequently consumed in larger portions sizes (in kcal).
DEVELOPMENT AND CHARACTERISTICS OF A FOOD IMAGE SET RATED FOR HEDONIC VALUE FOR USE IN NEUROIMAGING STUDIES. . ; 1Colorado State University, 2University of Colorado Denver
There is a need for food images for use in neuroimaging studies that are reliably rated for subjective hedonic value. Our primary aim was to develop a set of food images for use in fMRI research. The secondary aim of this study was to investigate relations among hedonic ratings of food images and participant characteristics (i.e. sex, weight & energy state). Participants (n=100; F=58, M=42) rated images of food for appeal and desire to eat on the computer program Imagerate©. Imagerate is specifically designed to assess hedonic ratings using a scale of 0-100. Participants also completed visual analog scales for hunger and were measured for height and weight. Images were collapsed into food categories and mean scores for appeal and desire to eat were computed for each category. Participant characteristics and visual analog scores were used to predict participants’ food ratings. Fruit was rated highest for appeal (71.8±11.9) followed by dessert/snacks (58.9±14.6), grains (57.5±13.8), dairy (56.9 ±13.2), vegetables (56.0±12.7), mixed dishes (55.6±14.1), and protein (53.7±17.4). BMI predicted ratings of food appeal in men (R2=.25, p<.01). Where as in women, hunger predicted ratings of food appeal (R2=.15, p<.05). These differences by sex were consistent across the food categories. Results from this study suggest that future neuroimaging studies consider such characteristics that may confound results of fMRI investigations.
CORTISOL AND GHRELIN FOLLOWING A LABORATORY STRESSOR IN OBESE NIGHT EATERS. ; NY Obesity Research Center
Stress responsivity is implicated in binge eating and bulimia nervosa, and may also contribute to night eating. Obese females (11 night eaters, NE; 17 non-night eaters, nonNE) participated in a cold pressor test (CPT). Groups were similar in age (29.7±7.8) and BMI (35.3±4.5). Ss placed one hand in ice water for 2min (0-2min), and blood was drawn at -10 (baseline), 0, 2, 5, 15, 30, 45 and 60min to obtain cortisol (n=28) and ghrelin (n=17). Appetite ratings preceded blood draws, and mean test time was 12:23±1h24min. Baseline cortisol was higher in NE (12.5±6.9µg/ml) than nonNE (6.7±4.30µg/ml; F(1,28)=7.5,p<.05), but ghrelin and hunger were not. Repeated ANOVA showed that CPT significantly increased both hormones, with peaks at 15min for each (cortisol F(7,182)=10.0,p<.01; ghrelin F(7,105)=2.2,p<.05); hunger also increased, peaking at 60min F(6,150)=10.5,p<.01). Area under the curve (AUC) in NE was greater for cortisol (593±277 NE, 351±229 nonNE; F(1,28)=6.3,p<.05), but the differences for AUC ghrelin (1827±524 NE, 1473±1031 nonNE) and AUC hunger (2454±2126 NE, 2269±1431 nonNE) were not significant. All results remained the same when controlling for test time, contraceptive use, depression score and binge eating status, but AUC results lost significance when controlling for respective baseline levels. The overall increase in ghrelin after CPT suggests ghrelin may complement cortisol action by promoting intake in stressful situations. This is the first demonstration of greater cortisol AUC after laboratory stress in NE, and implies a mediating role for cortisol in night eating.
PRIOR ACCESS TO A SWEET CUE IS PROTECTIVE IN FEMALES SELF-ADMINISTRATING COCAINE. . ; Penn State University College of Medicine
Preliminary data showed that female rats exhibit less avoidance of a saccharin conditioned stimulus (CS) when paired with passive administration (PA) of cocaine. We hypothesized that a similar pattern would be evident when saccharin was paired with self-administration (SA) and that less avoidance of CS intake would be associated with less cocaine SA. Saccharin was paired with SA of cocaine in male and female rats. Rats were given 5 min access to 0.15% saccharin followed by 1.5 h SA. During drug access, rats were placed on a FR10 schedule of reinforcement where completion of 10 licks on the active spout led to an iv infusion of cocaine (0, 0.16, 0.33, 0.66 mg/kg) for 16 days. Then, a progressive ratio test was conducted where the lick requirement increased by incremenents of 20. Break point occurred when 30 min elapsed without reward. As expected, cocaine suppressed CS intake. As occurred with PA, females exhibited less avoidance of the CS than males when paired with cocaine. Both males and females took more infusions of cocaine than saline (Males: 0.16 and 0.33 mg/kg > saline; Females: 0.33 and 0.66 mg/kg > Saline). However, females took less infusions of the 0.16 and 0.33 mg/kg doses than males. While females reportedly take more drug than males, this pattern is reversed when SA is preceded by access to saccharin. Females, then, may not simply be more sensitive to the rewarding properties of drug, but also to the reinforcing properties of natural rewards, and this increase in sensitivity to sweets may serve to protect against drug-taking behavior. This research was supported by DA09815.
HIGH-FAT DIET DURING PREGNANCY: LONG-TERM CHANGES IN FAT PREFERENCE, TRIGLYCERIDES AND OREXIGENIC PEPTIDES IN THE OFFSPRING. . ; Rockefeller University
This study tested whether
exposure to a fat-rich diet during pregnancy has long-term consequences in the
offspring. Four sets of dams, each with 2 groups maintained on either a
high-fat diet (HFD, 50% fat) or balanced diet (BD, 25% fat), were tested. For
the first 2 sets, the dams were given these diets from embryonic day 6 to
postnatal day 15 (E6-P15), with the HFD rats switched to a BD at P15, and the
offspring were examined at maturity (day 70) or before weaning (P15). At
maturity, the offspring exhibited a significant increase in body weight, fat
mass, and preference for a fat-rich diet, along with elevated levels of
triglycerides (TG) and leptin and increased expression of galanin (GAL) and
enkephalin (ENK) in paraventricular nucleus and orexin in perifornical hypothalamus.
Similar disturbances in TG and peptides were detected in HFD pups before
weaning (P15), when they were still normal in body weight. For the second 2
sets, dams had these diets from E6 to birth (E6-P0), with the HFD pups at birth
cross-fostered to dams on the BD, and then the pups of both diet groups were
examined either at P15 or day 70. Exposure to the HFD during the prenatal
period (E6-P0) produced a phenotype in these cross-fostered offspring similar
to that observed in rats with continued access to the HFD until P15. These
results show effects of the dam’s exposure to HFD on the offspring, which: a)
occur prenatally, b) persist beyond period of diet exposure; c) involve early
changes in TG and peptides that promote overeating of fat-rich diets, and d) lead
to dietary obesity.
DRIVE FOR THINNESS IS NOT THE SAME AS DRIVE TO BE THIN: ON THE MOTIVATION FOR DIETING IN NORMAL WEIGHT RESTRAINED EATERS AND BULIMIC INDIVIDUALS. ; Drexel University
Drive for thinness has been implicated as an etiological factor in the development of disordered eating. However, measures of this construct, such as the EDI-2 Drive for Thinness scale (DFT), appear to measure a desire to be thinner, but not the radical dieting mentality thought to contribute to disordered eating. This study developed a Drive to be Thin (DTBT) scale to assess desire to be objectively thin (15% below ideal BMI) and exclude items regarding avoidance of weight gain. DTBT items were judged for suitability by eating disorder experts and Cronbach’s alpha was calculated (∞=.947).
The association between DTBT, DFT, and fear of fatness (GFFS) as motivations for dieting was investigated in 64 unrestrained and restrained eaters (RE,URE) identified by the Herman and Polivy Restraint Scale and 22 females with Bulimia Nervosa (BN). A mixed model ANOVA revealed a significant interaction between group and motivation to diet.
DFT and GFFS were greater in REs compared to UREs, while DTBT was low in both. The traditional assumption that REs drive for thinness reflects an unhealthy need to be thin appears to be incorrect. Instead, REs appear to be motivated to diet mostly by GFFS. This is consistent with a predisposition toward weight gain in REs and our proposed hypothesis that restraint represents a proxy risk factor for weight gain. DTBT and GFFS were greater in BN, suggesting that BN are highly motivated by both, unlike REs who are only motivated by GFFS. A fear of fatness and drive to be thin may motivate unhealthy dieting and eating disordered behavior in BN.
ESTIMATION OF BLOOD GLUCOSE LEVEL BY OBJECTIVELY VALIDATED FEELINGS YIELDS A HOMEOSTATIC MODEL OF EATING. . ; 1University, 2University
Subjects consisted of 23 overweight (OW) adults and 40 normal weight (NWHBG) adults who reported higher weekly average blood glucose (BG) than 81.8 mg/dL (cut off) before the three daily meals by diary and 26 NWLBG adults with BG below cut off. All were motivated by functional intestinal disorders. During training, all subjects validated their feelings of initial hunger by concurrent blood glucose measurement. Subjects then used initial-hunger as a meal-start signal. In hospital, the trained subjects experienced initial hunger between 87 mg/dL and 60 mg/dL BG before breakfast, and concurrently estimated their BG with an estimation error of 3.2% ± 2.4% of the measured value. Over 5 months 23 OW subjects and 40 NWHBG significantly decreased BG (P <0.03), decreased energy intake by -697±471 and -581±549, and body weight by -6.7±4.7 and -2.5±4.6 (P <0.05), respectively. 26 NWLBG subjects maintained BG below cut off and showed no change in energy intake and body weight after training. With this training, the subject knew BG levels in spite of wide variation in energy expenditure during the day, obtained a meal by meal energy balance by reaching the same BG level before meals, and decreased insulin resistance, thus yielding a homeostatic model of eating. This learned eating behavior can adapt daily energy consumption to individual energy requirements and may be considered to complement general guidelines on nutrition.
A RELIABLE MODEL OF BINGE EATING IN RATS. ; Dept. Exp. Med. Pub. Health, Univ. Camerino
Combining repeated caloric restrictions and electric foot-shock stress has been shown to induce binge eating in rats (Hagan et al., Physiol & Behav; 2002), however in our laboratory we were not able to reliably obtain binge eating by combining these two determinants. In the present study caloric restriction was combined with a different stress, related to lack of control over environmental circumstances: female rats were allowed to see and smell palatable food (PF), but were prevented from access to it for 15 min.
Rats were divided in 4 groups and exposed to 3 consecutive 8-day cycles followed by the final test on day 25: a) the control group had chow ad libitum for 4 days, on days 5-6 they received PF (2h) and chow; on days 7-8 they had chow ad libitum; b) the second group had chow restricted to 66% of their normal intake for 4 days, was offered chow and PF (2h) on days 5-6 and only chow on days 7-8; c) the third group had chow and PF as controls, but on the test day (day 25) they had the stressful experience; d) the fourth group had chow restriction and on day 25 the stressful experience. On day 25 free access to PF and chow was offered and their intake was measured up to 24 h.
Food restriction or stress alone did not significantly increase PF in comparison to controls. Combining food restriction and the stress procedure on day 25 markedly and significantly increased PF intake. Administration by gavage of fluoxetine or topiramate significantly reduced PF intake.
The present method induces a marked and reliable increase in PF intake in female rats, that apparently mimics a condition of loss of control over it.
EATING BEHAVIOUR IN RESPONSE TO FOOD-CUE EXPOSURE: EXAMINING THE CUE-REACTIVITY AND COUNTERACTIVE-CONTROL MODELS . ; Maastricht University
Restrained eaters eat more after exposure to food cues (eg Fedoroff et al 1997), which fits with the predictions of the cue-reactivity model (Jansen 1998). However, Fishbach and colleagues (2003) reported that exposure to fattening foods can activate dieting goals. These results fit with the predictions of the counteractive-control model (Trope & Fisbach 2000), which states that exposure to temptations activates higher-order goals. Attempting to consolidate these divergent findings, we hypothesized that the salience of the food cue could represent a critical factor. We predicted that focusing attention on salient food cues would result in increased intake (cue reactivity) in restrained eaters, whereas exposure to an incidental food cue would result in decreased intake (counteractive-control), relative to controls. We employed a 3 (attended, incidental, vs control cue) X 2 (restrained vs unrestrained eaters) design. As expected, restrained eaters who attended to a food cue ate more than did restrained and unrestrained eaters in the control condition and unrestrained eaters in the attended-cue condition; however, the intake of restrained eaters exposed to the incidental cue did not differ from restrained or unrestrained eaters in the control condition. It appears that the manner of food-cue presentation may be critical in determining eating behaviour - attending to direct food-related cues disinhibits restrained eaters, whereas the presence of incidental food cues in the environment apparently does not disinhibit the eating of restrained eaters (and may activate dieting goals).
GASTRIC IRRITATION DOES NOT INDUCE NAHCO3 INTAKE.. ; UNESP
Rats with acute cell-dehydration induced by intragastric (ig) load of hypertonic NaCl ingest NaHCO3 in addition to water (five-bottle test). Moreover, it is known that hypertonic NaCl is a gastric irritant, so the aim of the present work was to investigate if the NaHCO3 intake occurs as a result of gastric irritation, comparable to a self-medication behavior. Adult male Holtzman rats (n=4-5) had ad libitum food, distilled H2O (dH2O) and two mineral solutions: 0.01 M KCl and 0.15 M NaHCO3 (three-bottle test). Water and mineral solution intake was recorded in rats treated with ig load of 2 M NaCl combined with prior dH2O (control group) or the gastric mucosa protective agent Al(OH)3 (2 g/kg of body weight) or in rats treated with ig load of other gastric irritants (50% ethanol, 0.6 N acetic acid). Rats pre-treated with Al(OH)3 increased water intake (8.8±1.5 ml, vs. control: 2.5±1.0ml/120 min) without significant changes on the ingestion of 0.01 M KCl (1.2±0.6, vs. control: 2.3±1.0 ml/120 min) or 0.15 M NaHCO3 (3.5±1.6 ml, vs. control: 5.9±3.5 ml/120 min). Ethanol or acetic acid induced no significant ingestion of water (0.1±0.1 and 0.2±0.1 ml, respectively), 0.01 M KCl (0.1±0.0 and 0.0±0.0) or 0.15 M NaHCO3 (0.2±0.1 and 1.0±0.5 ml). The results suggest that NaHCO3 ingestion is rather consistent to cell dehydration-induced by ig load of hypertonic NaCl than to a self-medication behavior.
Supported by: FAPESP, CNPq
EFFECT OF POST-NEONATAL THYMECTOMY ON BODY WEIGHT GAIN IN SWISS MICE. THE ROLE OF REGULATORY T-CELLS AND THE HYPOTHALAMIC ARCUATE NUCLEUS. ; 1Appareil Digestif Environnement Nutrition Laboratory (ADEN EA3234) Rouen University & Hospital & IFRMP23, 2Department of Molecular Medicine and Surgery, Karolinska Institutet, 3Immunopathology Laboratory (Inserm U905) Biomedical Research Institute Rouen University & Hospital & IFRMP23, 4Department of Neuroscience, Karolinska Institutet
Thymectomy (Tx) at 2-nd day after birth in mice prevents the development of regulatory
T-cells (T-regs) resulting in various autoimmune conditions sometime accompanied by wasting syndrome depending on genetic background. This suggests that in the early postnatal period, perturbations in the immune system may interfere with the establishment of the brain control of body weight, but the underlying mechanisms are unknown. In the present work we studied effect of post-neonatal Tx on body weight gain in Swiss mice. In contrast to the expected wasting syndrome, at 28 days after Tx, Swiss mice showed increased body weight vs. sham operated mice (21.6±0.6g vs. 18.5±0.5g, p<0.02) but lower number of T-regs as revealed by flow cytometry of Foxp3, a specific marker of T-regs. No inflammation was detected in the colonic mucosa of Tx mice. A preliminary immunohistochemical analysis of the Tx brains showed a decrease in α-melanocyte-stimulating hormone (α-MSH)-positive terminals in the hypothalamus but accumulations of α-MSH in cell bodies of the arcuate nucleus as well as activated microglia in the median eminence. These data suggest that the immune system may interfere with the establishment of the brain control of body weight acting via the arcuate nucleus.
THE EFFECTS OF OVERFEEDING AND PROPENSITY TO WEIGHT GAIN ON THE NEURONAL RESPONSES TO VISUAL FOOD CUES . ; University of Colorado Denver
Environmental visual cues are one of the first and primary inputs signaling the potential availability of food. The objective of this study was to examine the effects of short-term overfeeding on the neuronal responses to food-related visual stimuli in obese-prone (OP) and obese-resistant (OR) individuals. 19 reduced-obese, OP (10 women, 9 men) and 25 thin, OR (13 women, 12 men) individuals were studied. Functional magnetic resonance imaging (fMRI) was performed after two days of eucaloric energy intake and after two days of 30% overfeeding in a counterbalanced design. FMRI was performed while subjects were presented visual stimuli of 3 different categories: neutral control objects, neutral foods (NF), and foods of high hedonic value (HF). In the eucaloric state, food images, in general, elicited activation of insula in both groups. HF elicited activation of inferior temporal and posterior parietal cortices in both groups, consistent with increased attention to HF. Overfeeding completely attenuated these responses in OR while this activation persisted in OP. In OR, HF elicited activation of the hypothalamus which was inhibited with overfeeding. In OP, HF elicited activation of prefrontal cortex (PFC) in response to HF with overfeeding resulting in dorsolateral PFC activation. These findings emphasize the important role of attention to environmental visual cues and suggest that there are important phenotypic differences in the interactions between external visual sensory inputs, energy balance status, and brain regions important in the regulation of energy intake.
THE ROLE OF HYPOTHALAMIC MTORC1 SIGNALING IN DIET-INDUCED OBESITY . ; 1INSERM, U 862, 2University of Cincinnati
The mammalian target of Rapamycin (mTOR) kinase is a key regulator of several cellular functions, including cell growth and differentiation. Because hypothalamic mTORC1 signaling has been implicated as a target of leptin in the regulation of energy balance, we investigated its role in obesity-induced leptin resistance. In contrast to rats maintained on a low-fat (LF) diet for 3 weeks, rats maintained on a HF-diet had no anorexic response to icv leptin. Western blot analysis revealed that leptin was unable to modulate hypothalamic mTORC1 signaling in the HF group, whereas it significantly induced phosphorylation of both S6 Kinase 1 (S6K1) and S6 ribosomal protein (S6) in the LF group. Similar to leptin, the cytokine ciliary neurotrophic factor (CNTF) induces hypophagia and increases STAT3 phosphorylation. CNTF and its analogue CNTFAx15 activate leptin-like pathways in the hypothalamus even in leptin-resistant states, including diet-induced obesity. Icv CNTFAx15 decreased 24-h food intake and body weight in rats on HF or LF diet and increased the phosphorylation of hypothalamic S6K1 and S6 in a comparable way on both diets. Mice lacking S6K1 (S6K1-/-) did not respond to the anorectic action of either leptin or CNTFAx15, implying a crucial role for S6K1 in modulating the actions of these two cytokines. Finally, exposure to HF diet decreased mTORC1 signaling within the hypothalamus. Thus, these findings strongly point to the possibility that reduced hypothalamic mTORC1 signaling contributes to the development of hyperphagia, weight gain and leptin resistance during diet-induced obesity.
ANXIOGENIC, OREXIGENIC AND METABOLIC EFFECTS OF HYPOTHALAMIC GHRELIN . ; Dept. Psychology, Reed College, 3203 Woodstock Blvd.
Ghrelin is a 28 amino acid acylated peptide and is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). The GHS-R is expressed in hypothalamic nuclei where it is colocalized with NPY neurons. Increasing evidence suggests that ghrelin is involved in the regulation of food intake and energy balance and that its effects on body weight appear to be due in part to altered metabolism and energy expenditure. In the present study we examined the effects of ghrelin on feeding and energy substrate utilization (respiratory quotient; RQ) following direct injections into multiple areas of the hypothalamus. Ghrelin was administered at dark onset at doses of 50-200 pmol and feeding or RQ measures were assessed over 4 h. Results indicated that ghrelin increased eating and RQ after injection into several sites, particularly the paraventricular (PVN) and arcuate nuclei (Arc). In addition to metabolic function, other recent work suggests that ghrelin may play a role in anxiogenic behavior. In our study, separate groups of rats were injected with vehicle, 50 pmol or 200 pmol and then placed in an elevated plus maze for 10 min. Each test was performed as a single trial per animal. Ghrelin significantly decreased the number of entries and time spent in the open arms of the maze after administration into numerous hypothalamic areas, including the PVN and Arc. These findings are consistent with the argument that ghrelin mediates neuroendocrine and behavioral responses to stress in addition to its role as a hypothalamic orexigenic peptide.
5-HT1A RECEPTOR AGONISM ALTERS THE OREXIGENIC AND ANXIOGENIC ACTIVITY OF GHRELIN . ; Dept. Psychology, Reed College, 3203 Woodstock Blvd.
Ghrelin is a peptide hormone produced and secreted by the stomach and by hypothalamic neurons. Medial hypothalamic injections of the neuropeptide increase food intake and elicit anxiogenesis. In contrast, other data suggest that activation of 5-HT1A somatodendritic autoreceptors increases eating and decreases anxiety. In the present study rats were injected with vehicle or the 5-HT1A receptor agonist 8-OH-DPAT (0-200 ug/kg SC), 20 min prior to paraventricular nucleus (PVN) injection of ghrelin (0-200 pmol). Rats (n=12) were then placed in an elevated plus maze for 10 min. Each test was performed as a single trial per animal. In separate groups of rats, 8-OH-DPAT was injected SC 20 min before PVN administration of ghrelin. Food intakes were then measured over 4 h. Ghrelin significantly decreased the number of entries and time spent in the open arms of the plus maze after administration into PVN. Pretreatment with 8-OH-DPAT attenuated the anxiogenic action. In contrast, systemic administration of 8-OH-DPAT poteniated the feeding stimulant effects of ghrelin. These findings suggest that ghrelin and serotonergic mechanisms interact in the neural control of eating and anxiety-like behavior.
THE EFFECTS OF EGG-BASED BREAKFASTS ON COGNITIVE PERFORMANCE IN YOUNG ADULTS. . ; 1Department of Psychology Tufts University, 2Nutrition and Neurocognition Laboratory, JM HNRCA Tufts University
Previous research shows that carbohydrate-based breakfasts have positive effects on cognition and blood glucose levels in comparison to eating no breakfast. The present research further examines the effects of the nutrient composition of a breakfast meal on mood and cognitive performance in young adults. In the first study, 60 participants consumed one of three breakfasts: Eggs, toast and orange juice; an isocaloric meal of cereal bars and orange juice; or no breakfast. Thirty minutes later, participants completed mood and hunger scales, and underwent a series of cognitive tests that included measures of vigilance, spatial and short term memory. There were no differences among the dietary groups for cognitive tests. For mood measurements, vigor was significantly decreased (p <0.05) following consumption of either the cereal-based or egg-based meal in comparison to eating no breakfast. There was a trend (p = 0.06) for confusion ratings to be higher in individuals eating an egg-based meal relative to those eating no breakfast, and there was a trend (p=0.06) for fatigue ratings to be higher in individuals eating a cereal-based meal relative to those eating no breakfast. Limitations of the first study include measurement at only one time point following a meal, a between-groups design for cognitive testing, and the use of orange juice, which may have contributed high levels of carbohydrate to the egg-based condition, thus reducing our ability to see differences among the conditions. A study is under way 1) using a within groups design, 2) using modified breakfasts to eliminate excess carbohydrates in the egg-based condition, and 3) examining the time course of blood-glucose elevations following a meal containing some fat and protein (eggs) in comparison to a cereal-based meal or nothing.
GHRELIN HAS STRESS-LIKE EFFECTS ON THE BRAIN: A FUNCTIONAL MRI STUDY IN HUMANS. . ; 1Montreal Neurological Institute, 2Unilever R&D
Ghrelin is a gut peptide and the most potent known appetite stimulant. We previously showed that it modulates the brain response to food cues in limbic areas. The current study was undertaken to see if the neuromodulatory effect of ghrelin was specific to food stimuli.
Twenty lean male subjects underwent two fMRI scans on different days, while they viewed images of food, scenery and facial expressions. Prior to each scan, subjects received intravenous saline or ghrelin (1μg/kg).
Ghrelin enhanced the response to food pictures in areas involved in the appetitive response to food cues: the amygdala, insula, OFC, and parahippocampal gyrus. These effects correlated with hunger and later recall of stimuli. In amygdala and insula, ghrelin increased the activation to negative faces (fear and disgust) and reduced the response to positively valenced faces (happy and neutral).
This bias towards negative affective stimuli is also seen in anxiety, stress and depression. Our results are thus in keeping with ghrelin’s putative anxiogenic effects. We suggest that ghrelin, which is released from the gut during stress, causes changes in brain function that are associated with a feeling of anxiety. The individual may learn through repeated experience that suppression of ghrelin secretion, by eating foods high in calories, can relieve some unpleasant effects of stress. This could provide a link between stress and obesity, and explain the phenomenon of comfort foods, where individuals “self-medicate” their anxiety by eating.
ARCUATE NUCLEUS DESTRUCTION DOES NOT BLOCK FOOD DEPRIVATION-INDUCED INCREASES IN FOOD FORAGING AND HOARDING. ; Department of Biology, Georgia State University
Neuropeptide Y (NPY) and agouti-related protein (AgRP), two factors well-known to stimulate food intake in a variety of species, applied centrally to Siberian hamsters increase foraging and especially hoarding more than food intake in Siberian hamsters. Both orexigenic peptides are expressed in the arcuate nucleus (Arc) and their synthesis increased with food deprivation including in Siberian hamsters, as is foraging and hoarding. Therefore, we tested whether destruction of Arc neurons blocks these ingestive behaviors. This was accomplished either by microinjecting NPY conjugated to saporin (NPY-SAP) bilaterally into the Arc, or neonatal monosodium glutamate (MSG) treatment in order to destroy the Arc NPY/AgRP neurons, albeit not completely selectively. For both methods Arc cellularity and NPY, Y1 receptor, TH and α-MSH immunoreactivity (ir) were significantly decreased, as was cellularity and TH-ir in the area postrema after MSG treatment. Surprisingly, food deprivation-induced increased hoarding was exaggerated ~100 % in both types of Arc destruction, but only at 1 h after refeeding. Y1-receptor-ir was increased by both treatments in Arc NPY projection areas (paraventricular nucleus and perifornical area) and, combined with remaining NPY inputs, could account for the exaggerated increase. The converging evidence from both Arc destruction methods suggests that an intact Arc is not necessary for food deprivation-induced increases in food foraging and hoarding. Funded by NIH R01 DK 78358.
BEHAVIORAL RELEVANCE OF ANGIOTENSIN II RECEPTOR INTRACELLULAR SIGNALING PATHWAYS. ; Department of Psychology, University at Buffalo
Angiotensin II (AngII)-induced water and NaCl intake is a classic model of hormonal control of ingestive behavior. In vitro studies have provided a wealth of information about the intracellular signaling pathways engaged by AngII receptors and indicate that the AngII type 1 (AT1) receptor stimulates PKC and MAP kinase activation. Less is known, however, about the role of these signaling pathways in AngII-stimulated behaviors. Recent experiments led to the hypotheses that PKC is required for AngII-induced water, but not NaCl intake, and that MAP kinase is required for NaCl consumption, but not water intake after injection of AngII. We conducted two separate experiments to test these hypotheses. First, we injected rats with AngII in the presence or absence of the PKC inhibitor chelerythrine. AngII reliably increased water and NaCl intake; however, rats that were pretreated with chelerythrine drank less water, but consumed AngII-like amounts of NaCl. In a separate experiment, rats pretreated with the MAP kinase inhibitor U0126 or vehicle drank similar amounts of water after AngII treatment, but U0126-pretreated rats drank markedly less NaCl than rats receiving AngII alone. These data support the working hypotheses and extend our earlier findings and those of others. Perhaps more importantly, these experiments demonstrate the remarkable diversity of peptide receptor systems and add support for the finding that intracellular signaling pathways can have divergent behavioral relevance.
EGM. is supported by a University at Buffalo Presidential Fellowship. Additional support from NIH award DK-73800 to DD.
HEDONIC OVEREATING: BUFFER OR CATALYST TO OTHER ADDICTIVE BEHAVIOURS?. ; York University
In a recent paper, we reported that obese adults had higher scores on a measure of addictive personality traits than those of normal weight. Research has also linked excessive food intake with other forms of compulsive consumption like shopping and gambling. By contrast, some have argued that overeating competes with pharmacologic agents for brain reward sites, and thereby serves as a buffer for the potential abuse of addictive behaviours. The aim of this study was to understand these associations more clearly by comparing an age and gender-matched group of normal weight and obese adults (25-45 yr) on a broad range of addictive behaviours. Using binary logistic regression, results indicated that the total score on a well-validated measure of addictive problems - summing across a broad range of additive behaviours - was higher in obese than normal weight adults. However, a more interesting finding emerged when the addictive behaviours were dichotomized as either substance-based (e.g. drugs, nicotine) or activity-based (e.g. shopping, sex). Obese individuals had lower scores on the substance scale but higher scores on the activity scale compared to the normal-weight participants. While these results help explain the inconsistencies linking overeating and addictive behaviours, we are still left with uncertainty about causality. One possibility is that some individuals have a psychobiological predisposition to find pleasure from less potent activators of brain reward pathways (activities like eating and shopping), while others are constitutionally prone to stronger stimuli (drugs like cocaine and nicotine) to achieve a similar degree of pleasure.
DIFFERENTIAL EFFECTS OF COMMON HEPATIC, GASTRIC, AND CELIAC BRANCH VAGOTOMY ON FOOD INTAKE AND PICA BEHAVIOR FOLLOWING CHEMOTHERAPY IN THE RAT.. ; Monell Chemical Senses Center
Vomiting, nausea, and anorexia are among the main side effects of anti-cancer
chemotherapies such as cisplatin. Cisplatin primarily acts on vagal afferents
to produce emesis, but how this drug generates nausea and anorexia is poorly
understood. Electrophysiology indicates that cisplatin activates vagal
afferents of the common hepatic branch (CHB). Rats, a non-vomiting species,
ingest kaolin clay (i.e., pica) when made sick by toxins. It has been
hypothesized that pica behavior may model emesis in the rat. These studies
examined the effects of CHB, ventral gastric (GAS), or celiac branch (CEL)
vagotomies on pica and anorexia produced by cisplatin in the rat. Apomorphine,
a centrally acting dopamine agonist which reliably produces emesis and/or pica,
was also assessed. Results showed that cisplatin-induced pica was suppressed
only by CHB vagotomy, and not by GAS and CEL vagotomy. Suppression of daily
food intake and body weight following cisplatin treatment was also blunted by
CHB ablation, but exacerbated by GAS or CEL vagotomy. No condition displayed
altered apomorphine-induced pica. The current work is the first to show effects
of vagal lesions on pica behavior in the rat. Our results clearly show that
only in CHB vagotomized rats is there a diminution in ingestive behaviors
indicative of cisplatin-induced sickness. This investigation may help to
delineate the physiology of pica and define the neural circuitry of malaise,
which may significantly impact cancer patients receiving potent
pharmacotherapy. Support: NIH DK065709 and DC000014.
INHIBITION OF ANGIOTENSIN CONVERTING ENZYME PROTECTS AGAINST DIET-INDUCED OBESITY IN RATS. ; 1University of Cincinnati, 2Department of Psychiatry
Increasing evidence suggests that the renin angiotensin system (RAS) contributes to the etiology of obesity. Specifically, it has been reported that the RAS is overactive in obese humans and rodents, and it has been suggested that interfering with RAS activity might be a treatment option for obesity. To evaluate the role of the RAS in the development of diet-induced obesity we examined body weight, body composition, food intake and glucose tolerance in rats given an angiotensin converting enzyme inhibitor (Captopril; ~50 mg/kg/day). Male Long-Evans rats were fed a high-fat diet and randomly assigned to two weight-matched groups. One group received Captopril in their drinking water at a concentration estimated to provide ~50 mg/kg/day. Captopril-treated rats gained significantly less weight than controls on the high-fat diet, and the difference was mainly attributable to differences in adipose mass. Furthermore, rats given Captopril ate significantly less high fat diet and had improved glucose tolerance compared to controls. To determine if Captopril causes animals to defend a lower body weight, animals in both groups were fasted for 24 hr and subsequently restricted to 20% of their daily intake for 2 days. When food was returned ad libitum, Captopril-treated and control rats returned to their respective body weights at a similar rate. Collectively, these results suggest that inhibition of the renin angiotensin system is protective against the development of diet-induced obesity. Support DK56863
EFFECTS OF MONOTONY AND VARIETY FOODS ON FEEDING BEHAVIOR IN HUMANS. ; Feeding Behavior and Nutrition Research Center, CUSur, Universidad de Guadalajara
Variety in foods characteristics is an important determinant for its consumption. Diverse studies have indicated that the subjects tend to consume more foods when there is variety of diets. The objective of this experiment was to evaluate effects of variety or monotony of food on feeding behavior. Sixteen participants were assigned randomly to 4 groups. The experiment consisted of 2 phases. First group was exposed to monotony condition in both phases. Second group was exposed variety condition in both phases. Third group was exposed in first condition to monotony followed of variety and the fourth group was exposed to variety condition followed of monotony. Results showed that: 1) First group consumed a smaller amount of foods in both phases in comparison with second group; 2) Food consumption of second group was greater during variety condition; 3) Third group increased its food consumption during the second phase; and, 4) Group 4, presented greater food consumption during second condition. The results suggest that variety of foods increases the answer of consumption, whereas it diminishes in monotony condition.
THE LATERAL PARABRACHIAL NUCLEUS CONTROLS HYPERTONIC, NOT ISOTONIC, NACL INTAKE.. ; 1UNESP1, 2UNESP1, 3INIMEC-CONICET2, 4INIMEC-CONICET2, 5USP3, 6UNESP1
Preference for NaCl solutions reaches its peak at isotonic concentrations in rats. The inverted “U” shape of the preference curve is similar for hydrated and sodium-depleted rats suggesting that mechanisms that control sodium intake act changing the amplitude, not the shape of the curve. However, it is possible that some inhibitory mechanisms, like those from the lateral parabrachial nucleus (LPBN), act preferentially on the hypertonic side of the curve. The present work tested this hypothesis by either pharmacological intervention or immunohistochemistry for immediate early gene (c-fos) expression in the LPBN using two different protocols, systemic furosemide combined with low dose of captopril (FURO/CAP) and sodium depletion induced by peritoneal dialysis (PD). Methysergide (serotonin antagonist) injected into the LPBN (n=7/group) had no effect on 0.15 M NaCl intake (methysergide: 19+5.2; vehicle: 19.3+4.2, ml/2 h), but it enhanced 0.3 M NaCl intake (methysergide: 16.6+3.5; vehicle: 6.6+1.5, ml/2 h) induced by FURO/CAP without changing FURO/CAP-induced thirst. The number of positive cells for c-fos protein in the LPBN of rats made hypovolemic by PD enhanced when they ingested hypertonic (42+10 vs. hydrated: 18+1), but not isotonic (27+10 vs. hydrated: 20+8) NaCl. The results suggest that the LPBN has a preferential control over hypertonic rather than isotonic NaCl intake.
Supported by: CNPq, CONICET, FAPESP, PROSUL
INTERACTION BETWEEN CHOLECYSTOKINERGIC AND OPIOIDERGIC MECHANISMS OF THE LATERAL PARABRACHIAL NUCLEUS IN THE CONTROL OF NACL INTAKE. ; Department of Physiology and Pathology, School of Dentistry, UNESP
Bilateral injections of proglumide, a cholecystokinin (CCK) antagonist, into the lateral parabrachial nucleus (LPBN) increase 1.8% NaCl intake induced by sc furosemide (FURO, 10 mg/kg of body weight) combined with captopril (CAP, 5 mg/kg). The opioidergic agonist beta-endorphin into the LPBN induces 1.8% NaCl intake in satiated and normovolemic rats, an effect abolished by the opioidergic antagonist naloxone. In the present study we investigated the effects of naloxone alone or combined with proglumide into the LPBN on water and 1.8% NaCl intake induced by FURO + CAP. Male Holtzman rats (n=10) with cannulas implanted bilaterally in the LPBN were used. Bilateral injections of proglumide (50 μg/0.2 μl) into the LPBN increased FURO + CAP-induced 1.8% NaCl intake (23.2 ± 3.5 vs. veh.: 9.9 ± 1.8 ml/2 h), while naloxone (40 μg/0.2 μl) alone into the LPBN did not change NaCl intake. Naloxone into the LPBN partially reduced the effect of proglumide on FURO+CAP-induced 1.8% NaCl intake (16.6 ± 3.3 ml/2 h). Proglumide or naloxone alone or combined into the LPBN did not change FURO+CAP-induced water intake. The results suggest that the increase in FURO+CAP-induced sodium intake produced by the blockage of CCK receptors in the LPBN is partially dependent on the activation of opioidergic mechanisms in the same area.
Supported by FAPESP and CNPq.
SNP ANALYSES OF POSTPRANDIAL RESPONSES IN (AN)OREXIGENIC HORMONES AND FEELINGS OF HUNGER REVEAL LONG-TERM PHYSIOLOGICAL ADAPTATIONS TO FACILITATE HOMEOSTASIS. ; Maastricht University, Human Biology
Food intake regulation was previously shown to be partly under genetic control. This study aimed to determine whether the postprandial responses in plasma peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and ghrelin levels as well as feelings of hunger and satiety are associated with single nucleotide polymorphisms (SNPs) in relevant genes (N=103; age 31±14 years; body mass index (BMI) 25.0±3.1 kg·m-2). Dietary restraint, disinhibition and perceived hunger were determined using the three-factor eating questionnaire (TFEQ). The postprandial response in plasma ghrelin was associated with SNPs in PYY and LEPR (P<0.01), and in plasma PYY with SNPs in GHRL and GHSR (P<0.05). The postprandial response in feelings of hunger was characterized by a SNP-SNP interaction in LEPR and NPY2R (P<0.05). Dietary restraint and disinhibition were associated with a SNP in GHSR, perceived hunger with SNPs in GHSR and NPY (P<0.05). Surprisingly, subjects genetically vulnerable to overeating or a high BMI showed SNP associations with postprandial hormone concentration changes counterbalancing their genetic predisposition. These physiological adaptations facilitate homeostasis. Reinforcements of direct genetic effects were observed as well. SNP-SNP interactions in addition to the conventional single-SNP associations elucidated findings that were otherwise inexplicable.
MAPPING OF G-PROTEIN COUPLING REVEALS A CRITICAL AREA FOR MU-OPIOID RECEPTORS IN THE MEDIAL SHELL OF THE NUCLEUS ACCUMBENS IN MODULATING INTAKE OF STANDARD AND PALATABLE FOOD . ; Drexel University Coll Med
Mu-opioid receptors (MOPRs) within the nucleus accumbens (NAcc) have been regarded as modulators of the affective aspect of food intake. Within this heterogeneous region, MOPRs are reported to be especially involved in the hedonic evaluation of energy-dense, presumably palatable foods. Here, we aim to determine the effect of MOPR blockade on food intake using the MOPR antagonist, β-funaltrexamine (β-FNA). We administer β-FNA (3.2nmol/0.2µl/side or 8nmol/0.5µl/side) into different coronal levels of the NAcc medial shell of rats. Furthermore, we compare the effect of ß-FNA within a single region of the NAcc medial shell on consumption of standard chow and a highly palatable diet containing sucrose and fat. B-FNA decreased consumption of the palatable diet only within a confined rostrocaudal region of the NAcc. In contrast, MOPR-stimulated G-protein coupling measured by [35S]GTPγS autoradiography was decreased in all coronal groups. Thus, although ß-FNA decreased coupling in the Nacc medial shell across the entire rostrocaudal axis, this effect was only associated with decreased feeding in a restricted rostrocaudal region. Moreover, ß-FNA's hypophagic effect was not diet selective within this region. ß-FNA decreased the intake of standard and palatable chow suggesting the anorectic effect of MOPR blockade is not sensitive to the diet’s sensory properties. Thus, NAcc MOPRs may be involved in a more general role in the consumption of all foods. USPS DK067648 to KJS
PROGRAMMED ALTERATION OF HYPOTHALAMIC LEPTIN AND INSULIN SIGNALING PATHWAYS CONTRIBUTES TO REDUCED ANOREXIGENIC RESPONSES IN IUGR OFFSPRING . ; Harbor-UCLA Med. Ctr. Ob/Gyn
OBJECTIVE: Maternal food
restriction (FR) results in IUGR newborns that develop hyperphagia and adult
obesity. Central anorexigenic basal leptin and insulin signal molecules
are downregulated in IUGR newborns. Leptin acts via JAK-STAT3 and insulin-PI3K
pathways. We studied the response of hypothalamic leptin/insulin signal
molecules to peripheral leptin.
METHOD: Rats received ad
libitum food (Control) or were 50% FR during pregnancy (e10 to 21). 1 day old
males received saline or leptin (1μg/g, i.p). Hypothalamic protein expression
was determined at 15, 30 and 45 minutes of total STAT3, phosphorylated STAT3
(pSTAT3), inhibitor of leptin signal (SOCS3), insulin substrate (IRS2), AKT and
pAKT. Data is compared between leptin and saline treatments.
RESULT: In response to
peripheral leptin, IUGR newborns show marked dysfunction in hypothalamic
signaling responses. (1) JAK-STAT3: Leptin-treated Controls show progressively
increased pSTAT3 with initial suppression of SOCS3 than saline-treated
Controls. In leptin-treated IUGR, there is sustained decline in pSTAT3 level
with failure to downregulate SOCS3. (2) PI3K: Leptin-treated Controls show
significantly reduced IRS2 and pAKT than saline-treated Controls. However,
leptin-treated IUGR newborns exhibit a paradoxical increased IRS2 and pAKT.
CONCLUSION: IUGR offspring
show reduced pSTAT3 response in conjunction with enhanced SOCS3 response. The
persistent increase in insulin responses indicates a dysfunction in dynamic
signaling, leading to altered anorexigenic response and development of
GHRELIN'S ROLE IN FEEDING BEHAVIOR AND MEMORY PERFORMANCE.. ; Yale University Depts Ob/Gyn & Reproductive Sciences and Neurobiology
The gut hormone, ghrelin, exerts its effect on the brain by regulating neuronal activity. Ghrelin-induced feeding behavior is controlled by the acuate nucleus neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons. Our recent studies have shown that the mechanism by which ghrelin alters NPY/AgRP neuronal activity is uncoupling protein 2-(UCP2)dependent and is driven by a hypothalamic fatty acid oxidation pathway involving AMPK, CPT1 and free radicals. In addition to the hypothalamus, we have also shown that ghrelin regulates neuronal activity in other brain regions including the telencephalon where ghrelin binding was observed. We found that circulating ghrelin enters the hippocampus and binds to neurons of the hippocampal formation, where it promotes dendritic spine synapse formation and generation of LTP. These ghrelin induced synaptic changes are paralleled by enhanced spatial learning and memory. Targeted ghrelin gene disruption resulted in lower spine synapse number in the CA1 region and impaired performance of mice in behavioral memory testing, both of which were rapidly reversed by ghrelin administration. Our observations reveal an endogenous function of ghrelin connecting metabolic control with higher brain functions and suggest novel therapeutic strategies to enhance learning and memory processes.
INDIRECT ACTIVATION OF PARABRACHIAL CB1RS BY BLOCKADE OF AN ENDOCANNABINOID DEGRADATIVE ENZYME SELECTIVELY STIMULATES FEEDING OF PALATABLE FOOD. ; Drexel University Coll. Med., Dept. of Pharm/Phys
These studies investigated roles for endocannabinoids (EC) in the parabrachial nucleus of the pons (PBN) in controlling feeding. By immunocytochemistry, we visualized the EC degradative enzyme, fatty acid amide hydrolase (FAAH) throughout the PBN. Inhibition of FAAH by infusing arachidonoyl serotonin (AA5HT) bilaterally (4 nmol/0.5 μl/side) into the lateral PBN increased consumption of pellets high in fat (60% of total kcal) and sucrose (7%). During the 4-hr test, rats ate 68.7±7.5kcal after inhibitor compared to 48.2+/-3.8 kcal after vehicle; p<0.05. Notably, the rats compensated for this intake by reducing consumption of standard chow (from 43.2±6.4 to 18.1±4.1; p<0.01) during the subsequent 20hrs. Thus, rats treated with FAAH inhibitor shifted their 24-hr intake towards the more palatable diet. Although AA5HT has no direct effect on CB1Rs, the hyperphagic responses were indeed mediated through CB1Rs, as the selective CB1R antagonist, AM251 blocked the hyperphagic action of the inhibitor (veh, 47.4±4.7; AA5HT, 71.5±7.8; AM251, 43.5±4.1; AA5HT and AM251, 47.5±5.9 kcal). Additionally, in separate groups of animals, AA5HT increased 24-hr intakes of high fat/sucrose pellets when given alone (110.6±9.6 to 139.9±13.3; p<0.01), but failed to alter 24-hr intakes of standard chow (88.8±4.5 to 86.8±13.8). This work strongly suggests a physiological role for parabrachial cannabinoid mechanisms in modulating intake of foods with hedonically-positive sensory properties.
THYLAKOIDS PROMOTE SATIETY IN HEALTHY INDIVIDUALS. ; 1University, Experimental medical Science, 2University Hospital, 3University, Chemical Center, 4University Hospital
Background: Appetite control for palatable food is easily
disrupted, satiety signals not being strong enough to prevent further eating in
the face of a highly rewarding food. Fat is easily overconsumed in a process named passive overeating. We have found that a delay of fat digestion promotes satiety for fat, leading to decreased food intake and body weight in rat and mouse. In this study we report a similar satiety induction in man. The delay of fat digestion was induced by the addition of compounds from green leaves, thylakoids, that retard fat digestion through steric hindrance of pancreatic lipas/colipase.
Results: Thylakoids were isolated from spinach. 11 normal weight
healthy persons were given a standard meal with and without thylakoids after
overnight fast. Blood samples were withdrawn during six hours after start of
eating and various appetite regulating hormones measured. Thylakoids when added
to a meal caused a significant elevation of CCK concentrations postprandially,
especially at time points between 3 and 6 hours. Ghrelin concentrations were
significantly reduced as was insulin levels during the first two hours. Leptin
levels were raised at time point 6 hours.
Conclusions: The consumption of refined palatable food could be controlled by the addition of compounds that retard fat digestion, without causing steatorrea. The prolonged time for digestion, evidenced by stimulation of CCK especially in combination with leptin may be important for control of appetite.
OBESE BINGE-EATERS SHOW ALTERED GHRELIN AND LEPTIN LEVELS FOLLOWING BARIATRIC SURGERY.. ; University of Pennsylvania
This prospective study examined changes in weight, eating
behavior, and ghrelin and leptin levels in 36 extremely obese individuals (BMI
= 50.7 kg/m2) who underwent either Roux-en-Y-gastric bypass (RYGB)
or laparoscopic adjustable gastric banding (LAGB). Before surgery, 14 pts were
diagnosed with binge eating disorder (BED), while the other 22 had no symptoms
of BED. As expected, RYGB pts lost significantly (p <0.001) more weight
than LAGB patients at both 2 and 6 mo (M) following surgery (24.2 vs 11.7% at
M6). No significant differences in weight loss were found between BED vs.
non-BED pts at 2M, but non-significant trends towards smaller weight losses in
BED pts emerged at 6M in the LAGB group (12.8 vs 9.8%). The % of BED pts
reporting any binge episodes within the last 28 days declined from 98% at
baseline to 7% at M2 and 0% at M6; surgery type did not affect amelioration of
binge eating. At M2, significant reductions in fasting ghrelin levels were
found in RYGB patients, in contrast to the significant increases in ghrelin in
LAGB patients (-8.7% vs +9.4%, p <0.05). Interestingly, BED-LAGB pts had
larger increases in ghrelin than non-bingeing LAGB patients (21.5 vs 3.5%,
p<0.05) at 2M, despite no significant differences in weight lost at 2M. All
groups showed significant reductions in fasting leptin levels 2M after surgery
except BED pts undergoing LAGB. These results support the hypothesis that
patients with BED show abnormal hormonal profiles after bariatric surgery,
particularly following LAGB. These hormonal differences did not affect weight
loss at 2M, but may attenuate weight loss over time, as suggested by M6 data.
The data provide preliminary evidence that BED pts may be more successful with
RYGB than LAGB, though further study is clearly needed.
SATIETY SIGNALS FROM THE GUT . ; University of Adelaide Discipline of Medicine, Royal Adelaide Hospital
The gastrointestinal (GI) tract plays a vital role in the regulation of energy intake. While a high dietary fat intake leads to overconsumption, fat also has potent effects on those GI functions that favour the suppression of energy intake. The presence of fat in the small intestine slows gastric emptying, distending the stomach and increasing fullness, and associated with the modulation of motor patterns in the GI region, particularly stimulation of pressures in the pylorus. Interaction of fat with small intestinal receptors also triggers the release of gut hormones, including CCK, PYY and GLP-1, and the suppression of ghrelin. All these changes are thought to contribute to the suppression of energy intake. The effects of fat on energy intake and GI function are abolished when fat digestion is inhibited and dependent on fatty acid chain length as well as the length and/or region of intestine exposed to nutrient. - An important role for distal small intestinal feedback is demonstrated by the success of gastric bypass surgery, directing nutrients to the distal gut, in accomplishing significant weight loss. GI function can adapt to excess nutrient exposure, rendering it less sensitive to nutrient and/or hormonal stimuli. Since obese individuals have an increased energy/nutrient intake, they may have a reduced ability to sense gut stimuli, associated with reduced modulation of gut functions, thus, compromising their capacity to limit their energy intake. Strategies are required to stimulate those aspects of GI function that are associated with the suppression of energy intake, ultimately resulting in sustained weight loss in obesity.
RATS DO NOT INTERRUPT FOOD CONSUMPTION TO REACT TO NOXIOUS HEAT STIMULATION. ; Department of Neurobiology, University of Chicago
This study aimed to identify key factors that affect the selection between ingestion and responding to a noxious stimulus. Experiment 1 examined if this selection is impacted by appetite, and the palatability and nutritive content of the food. Intraoral infusions of neutral (water) or palatable and preferred (sucrose and saccharin) solutions suppressed paw withdrawals to the same extent as occurred when rats ate chocolate, showing that suppression occurs even when ingestion is induced and when the food has no caloric value. In contrast, ingestion of non-preferred (salt) or aversive (quinine) solutions produced no withdrawal suppression. During chocolate ingestion, paw licks were almost completely suppressed, presumably because paw-licking would require putting down the chocolate morsel. Paw licks were partially suppressed during intraorally-induced ingestion of water, sucrose, and saccharin, and not suppressed during ingestion of salt or quinine. In experiment 2, the impact of nausea on the defense of eating was tested. During chocolate ingestion following infusion of neutral (water) or non-preferred (salt) solution, paw withdrawals and licks were suppressed. Interruptions to eating were brief and comparable to those seen during chocolate ingestion without any infusions. However, during chocolate eating following quinine infusion, paw withdrawals to noxious heat were no longer suppressed and eating was interrupted for a longer time. Yet, paw licks remained suppressed. Thus, although rats ate with hesitation following possible quinine-induced nausea, they were reluctant to relinquish their chocolate.
SEX DIFFERENCES: BEHAVIORAL, METABOLIC AND STRESS CONSEQUENCES OF A FEMALE BIAS VISIBLE BURROW SYSTEM. ; University of Cincinnati
The visible burrow system (VBS) is an ethological model used to investigate effects of social stress consequential of hierarchy formation. Previous studies have characterized behavioral and physiological differences resultant of dominant (DOM) / subordinate (SUB) formation, but only in male rats. Female social behavior and ensuing physiological alterations have not been investigated. Here we ask, will female rats form a hierarchy similar to males resulting in decreases in body/lipid mass, insulin and leptin and increases basal corticosterone in SUB? This was accomplished via 14 day interaction in female bias colony consisting of 4 females and 2 males, controls are shared cage female and male. Restraint stress test was given to females on day 13. Females, although not as aggressive as males, formed a hierarchy with DOM displaying offensive behaviors (chasing, on-top-of and chamber guarding) and SUB defensive behaviors (flight and on-the-back). Unlike males, females, regardless of status, did not have a decrease in body mass. SUB females gained body mass significantly faster than DOM females, whereas SUB males had significantly suppressed body mass compared with DOM and control males. The alterations in body mass are reflected in total fat pad mass in males with SUB having significantly decreased total fat mass compared with DOM and controls. In females, however, DOM have significantly increased total fat pad mass compared with controls. These data suggest social hierarchy behavior is similar among females and males, but physiological responses are opposing.
TARGETED ENHANCEMENT OF OLEOYLETHANOLAMIDE MOBILIZATION IN PROXIMAL SMALL INTESTINE INDUCES ACROSS-MEAL SATIETY IN RATS . ; 1University of California, Irvine, 2Italian Institute of Technology
Pharmacological administration of the natural lipid amide, oleoylethanolamide (OEA), inhibits food intake in rodents by prolonging latency to feed and post-meal interval. This anorexic effect is mediated by activation of peroxisome proliferator-activated receptors (PPAR-α). Food intake stimulates mucosal cells in duodenum and jejunum to generate OEA, suggesting that this lipid-derived messenger may act as a local satiety hormone in the upper proximal small intestine. As a test of this hypothesis, here we examined whether targeted enhancement of small-intestinal OEA production affects feeding behavior in rats. We constructed an adenoviral vector that directs overexpression of N-acylphosphatidylethanolamine-hydrolysing phospholipase D (NAPE-PLD), which catalyses the production of OEA from NAPE. Intraduodenal injection of this vector (Ad-NPLD) resulted in a time-dependent increase in NAPE-PLD expression and OEA production, which was restricted to the proximal small intestine. No such effect was observed after administration of control vector. Enhanced OEA mobilization in Ad-NPLD-injected animals was temporally associated with increased expression of two PPAR-α target genes (PPAR-α and CD36) and with decreased food intake. This hypophagic phenotype was attributable to increase feeding latency and post-meal interval, rather then decreased meal size. The results suggest that localized changes in small-intestinal OEA production are sufficient to induce in rats a state of across-meal satiety.
GENETIC DISSECTION OF HUMAN TASTE PERCEPTION . ; 1NIDCD/National Institutes of Health, 2Givaudan Flavors Corp.
Inherited variation is an important source of differences in human taste perception. The paradigm for this variation has been large differences in the perceived bitterness of thiol-containing compounds exemplified by phenylthiocarbamide and propylthiouracil (PTC and PROP). We found that these compounds are sensed through the bitter receptor encoded by the TAS2R38 gene, which exists in two major forms, designated the major taster and major non-taster alleles, in populations worldwide. We have extended these genetic methods to other taste modalities, and recently applied them to variation in sweet taste perception. A naturally occurring form of the TAS1R2 gene, differing from the most common form at 3 amino acid positions, confers a reduced sensitivity to sweeteners in in vitro assays. Mutagenesis studies combined with in vitro functional analysis allows dissection of the relative contribution the 3 variant amino acids to receptor function, and provides insights into the mechanisms of sweet receptor signaling. More broadly, genetic association studies with candidate genes reveal additional genetic contributions to variation in sweet perception, and suggest that genetic variation in non-protein coding regions make major contributions to this phenotypic variation in the population.
THE EFFECTS OF OLEOYLETHANOLAMIDE ON FEEDING BEHAVIOUR INVOLVE HYPOTHALAMIC OXYTOCIN NEURONS. ; 1Dept. of Human Physiology and Pharmacology, University of Rome La Sapienza, 2Dept. of Pharmacology, University of California, Irvine
Oleoylethanolamide (OEA) is the monounsaturated analogue of anandamide. Differently from anandamide, which causes overeating and stimulate lipogenesis by activating CB1 receptors, OEA decreases food intake and body weight gain in rats and mice through a cannabinoid receptor-independent mechanism. The effects of OEA on feeding are behaviourally selective and are due to the prolongation of feeding latency and post meal interval. A large body of evidence indicate that they are mediated by the activation of peripheral PPAR-alpha receptors, but the central mechanisms downstream to this activation are still unclear.
Data obtained mapping brain c-fos mRNA levels revealed that the systemic administration of OEA evokes highly localized increase of c-fos transcription in the the paraventricular nucleus (PVN) and the sopraoptic nucleus (SO). The magnocellular components of both nuclei release oxytocin, one of the anorectic hypothalamic neuropeptides, and we hypothesized that oxytocin neurons might play a key role in regulating energy intake after OEA administration.
In agreement with our hypothesis, we found that OEA enhances the gene expression of oxytocin in both areas and that its anorexiant action can be prevented by pretreatment with a selective oxytocin receptor antagonist. Our data suggest that oxytocin release in the PVN and SO nuclei may be involved in the mediation of the effects induced by OEA on feeding.
PERCEPTUAL AND AFFECTIVE PROCESSING IN APPETITE FOR FOODS. ; 1Psychology, University of Birmingham, 2Universität Tübingen
Work using rated appetite, intake tests and brain imaging on eaten, pictured or named foods has confounded multifarious social, somatic and sensory attributes of a nutrient (such as fat or sugar) and relied erroneously on mere wordings of ratings of appetite to distinguish hunger or its satiety from so-called palatability, pleasure or reward. We report processing of information from pictures of foods that varied independently in fat and sugar contents and in sizes of portions. Such stimuli still confound diverse signals from each source of stimulation but the mental processes may be distinguishable by scaling the individual’s discrimination of stimulus levels from the learnt norm, shown for the taste of sugars in rats at SSIB’s predecessor 40 years ago. This personal cognitive diagnosis is sharpened by processing-analytical ratings in addition to overall appetite for each food – in this experiment, attraction or repulsion (valence) and degree of interest (arousal). Controls for colour and shape were non-food objects. In both healthy people and patients with type 2 diabetes, fat contents of the pictured foods generally had the greatest impact on rating of appetite, with sugar contents often contributing substantially and portion size playing only minor roles. Individuals varied widely, sometimes also across subsets of pictures, between perceptual processing driven by sight of a food and affective processing, tapped by valence and/or arousal. Such data on the specifics of ingestive cognition are essential to regional connectivities in imaging.
SOUR AND SALTY TASTE: A PARAMETRIC STUDY. ; Feeding Behavior and Nutrition Research Center, CUSur, Universidad de Guadalajara
Chemical properties of food like flavor, texture or odor provide information to organism on convenience of eating or avoiding a specific food. Some flavors like sweet and salty are accepted by an innate preference. On the other hand, acid and bitter are avoided. An element to consider is the concentration of flavor since it is an important factor for acceptance or rejection of a food. The objective of this experiment was to evaluate the effects of different concentrations from acid and salty flavors, using chloride of sodium and citric acid. Sixteen Wistar rats, eight females and eight males, were divided in two groups. They were exposed to twelve concentrations of citric acid or sodium chloride. Each group was divided in two sub-groups of four subjects each one, to which the concentrations in ascending or descendent order were given to them. Results indicated that low concentrations of citric acid and sodium chloride were consumed in greater proportion than high concentrations. This confirms that a flavor that is accepted to low concentrations can be rejected in high concentrations.
GASTRIC ELECTRICAL STIMULATION REDUCES C-FOS EXPRESSION IN THE RAT NUCLEUS OF THE SOLITARY TRACT. ; Appareil Digestif Environnement Nutrition Laboratory (ADEN EA3234), Biomedical Research Institute Rouen University & Hospital & IFR23
Gastric electrical stimulation (GES) improves appetite, nausea and vomiting in patients with gastroparesis, but the underlying mechanisms are incompletely understood. It has been previously shown that GES reduces c-Fos expression in the corticotrophin-releasing factor-producing neurons of the hypothalamic paraventricular nucleus during post-operative ileus in rats. However, the effect of GES on the nucleus of the solitary tract (NTS) was not investigated. This study in rats aimed to determine the effect of 1 hour GES on i) the gastric emptying rate; and ii) the activation of neurons in the dorsal vagal complex. Two electrodes were implanted in the rat gastric atrium during laparotomy, then stimulation (amplitude: 5 mA; pulse duration 330 μs; frequency: 14 Hz; 0.1 sec ON/5 sec OFF) or sham stimulation (control group) were applied. Gastric emptying of a non caloric solution was measured by the phenol red method. Using immunohistochemistry, the number of c-Fos protein-expressing neurons were measured in the NTS. The rate of gastric emptying was not affected by 1 hour GES (57% vs. 61%). GES reduced the number of c-Fos-positive cells by 75.3% (p<0.05), 84% (p<0.001) and 93.8% (p<0.05) in caudal, intermediate and rostral NTS, respectively, while not modifying the number of c-Fos-labelled cells in the area postrema or in the dorsal motor nucleus of the vagus. These data show that GES reduces c-Fos expression in the NTS during post-operative gastric ileus in rats supporting its involvement in GES effects on the central nervous system.
IMPLICATIONS OF ARCUATE NUCLEUS ACC AND MALONYL-COA IN THE REGULATION OF ENERGY BALANCE. ; 1Johns Hopkins University School of Medicine, 2University of Alberta
Acetyl-CoA carboxylase (ACC) is a key regulatory enzyme of fatty acid biosynthesis (FAB). Accumulating evidence suggests that hypothalamic malonyl-CoA, the product of ACC and an intermediate of FAB, is a mediator in the regulation of body energy balance. Alteration of ACC activity in the arcuate nucleus (Arc), which modulates Arc malonyl-CoA level, is important in the regulation of energy balance. Fasting inhibits Arc ACC, which contributes to the lowered Arc malonyl-CoA level, while refeeding activates Arc ACC, which favors the increased Arc malonyl-CoA level. Thus, alterations of ACC activity in the Arc are physiologically relevant. Leptin, an anorexigenic hormone, increases Arc malonyl-CoA level through activating Arc ACC. ACC links AMP-activated kinase, an upstream kinase for ACC, and malonyl-CoA to mediate leptin intracellular signaling pathway in the Arc. Malonyl-CoA is a physiological inhibitor of carnitine palmitoyltransferase-1 (CPT-1) and CPT-1 has been proposed as a mediator downstream of malonyl-CoA signaling in the Arc. ICV oxfenicine, a potent and selective CPT-1 inhibitor, unexpectedly stimulates food intake and lowers malonyl-CoA level in the Arc. Such findings strongly challenge the view that CPT-1 inhibition is a downstream step in mediating the anorectic signaling pathway from ACC activation/malonyl-CoA increase. The recently discovered brain-specific isoform of CPT-1, CPT-1C, may act as an effector in relaying the signaling from ACC and malonyl-CoA in the Arc. In summary, alterations of ACC activity and malonyl-CoA level in the Arc are important in the regulation of energy homeostasis.
DISCONNECTION OF THE GUSTATORY THALAMOCORTICAL LOOP PREVENTS BOTH LEARNING AND MEMORY OF DRUG-INDUCED DEVALUATION OF A SWEET CUE.. ; 1PennState College of Medicine, 2Wesleyan College
Consumption of an highly palatable 0.15% saccharin solution, can be reduced when this gustatory conditioned stimulus (CS) is repeatedly paired with a drug of abuse, such as morphine or cocaine. We believe that this effect isn't due to the aversive, but to the rewarding, properties of the drug. Specifically, Grigson (1997) hypothesized that rats avoid intake of the CS because it is devalued in anticipation of the availability of the highly preferred drug of abuse. In support, we have shown that drug-induced suppression of CS intake, but not LiCl-induced conditioned taste aversion, is disrupted by bilateral lesions of the taste thalamus or taste cortex. The present study tested the hypothesis that neither nuclei alone, but the communication between the two structures is essential for drug-induced contrast. Specifically, we tested whether asymmetric lesions of the gustatory thalamocortical loop (THCx) would block retention of pre-operatively acquired saccharin-morphine avoidance and postoperative suppression of intake of a Polycose CS when paired with cocaine. The results of 1- and 2-bottle tests indicated that retention of a preoperatively acquired saccharin-morphine (15 mg/kg) pairings requires an intact thalamocortical loop, as do acquisition of a new Polycose-cocaine (10 mg/kg) association. These data show that the gustatory thalamocortical loop is essential to both acquisition and retention (i.e., both learning and memory) of a taste-drug association. This research was funded by DA12473 and DA17416.
PERIPHERAL AND CENTRAL CATECHOLAMINE DEFICITS IN PREADOLESCENT OBESITY-PRONE RATS . ; 1Tufts University School of Medicine, Department of Pharmacology and Experimental Therapeutics, 2Tufts University School of Medicine, Program in Neuroscience, 3Beth Israel Deaconess Medical Center, Department of Medicine
Since the first reports that dopamine in the nucleus accumbens is depressed in obese rats (Pothos et al., 1998, Appetite 31, 405) and mice (Fulton et al., 2006, Neuron 51, 811), corroborating evidence shows that activity in mesolimbic dopamine terminal regions is altered in individuals with leptin deficiency (Farooqi et al., 2007, Science 317, 1355) and that peptide YY and leptin may modulate mesolimbic systems (Batterham et al., 2007, Nature 450, 106; Grill et al., 2007, Cell Metab 6, 423). However, the developmental aspects and anatomical selectivity of the central dopamine deficiencies in obesity have not been understood. To determine whether differences in mesolimbic dopamine levels predate body weight differences in inbred obesity-prone and obesity-resistant rats, we measured electrically evoked dopamine release from nucleus accumbens slices of 4-week old female rats. The average body weight was not statistically different (79.9 ± 7.3 grams vs. 66.1 ± 4.4 grams). The mean evoked dopamine signal amplitude was 4.7 ± 0.3 pA in obesity-prone rats vs. 12.3 ± 1.9 pA in obesity-resistant rats (n=10-13, p<0.01). Therefore, predisposition to obesity is most likely “imprinted” in mesolimbic dopamine systems early in life. Furthermore, the amplitude of monoquantal adrenal chromaffin catecholamine release was 15 ± 0.4 pA in obesity-prone versus 14 ± 0.5 pA in obesity-resistant rats (n=6800 and 3900 quanta respectively). Central deficits in catecholamine neurotransmission appear to be selective as quantal size of catecholamine secretion in adrenal medullary chromaffin cells is similar in obesity-prone and obesity-resistant rat strains.
Supported by DK065872
ASSOCIATIONS BETWEEN STRESS, AWAKENING CORTISOL, ADIPOSITY, EATING ATTITUDES AND MACRONUTRIENT INTAKE IN MEN AND WOMEN. ; 1School of Human and Life Sciences, Roehampton University, 2Medizinische Klinik, Innenstadt Klinikum der Universität
We hypothesised involvement of cortisol in stress and eating. Salivary cortisol was measured immediately, 30 mins and 60 mins after wakening, (cortisol awakening response; CARi= incremental AUC; CARg= AUC over ‘ground’), in 29 women and 23 men. We sought correlations between CAR, adiposity, stress (Weekly Stress Inventory-Short Form) and eating attitudes (Revised Three Factor Eating Questionnaire), and macronutrient intake during that day. Correlations were adjusted for age, and considered separately for men and women. In men, but not in women, greater CARi was associated with higher eating restraint (partial r= 0.55 controlling for BMI), lower BMI (r= -0.56) and smaller waist (r= -0.50). In men also, more stressful events in the prior week, but not stress intensity, predicted greater CARi (r = 0.41) and saturated fat intake (%E; r= 0.38), whereas greater stress intensity was correlated with higher carbohydrate:protein ratio (%E; r= 0.44). In women, more stressful events predicted lower CARg (r= -0.52) and cortisol immediately after wakening (r= -0.47), while higher carbohydrate:protein ratio was correlated with reduced emotional (r= -0.40) and uncontrolled eating (r= -0.39) but not with stress, although emotional eaters reported greater intensity of stressful events. Associations between stress, cortisol, adiposity and diet differ by sex, but CAR did not predict that day’s diet.
OVEREATING BY SWEETENING A FAT-RICH FOOD: INDEPENDENCE FROM POSTINGESTIVE CHOLECYSTOKININ AND INSULIN RELEASE. ; School of Human and Life Sciences, Whitelands College, Roehampton University
We hypothesised that sweetness may stimulate excess consumption of a fat-rich food by inhibiting release of the satiety hormone, cholecystokinin (CCK). After a 6-hr fast, healthy adults ate fat-supplemented yoghurt (100 g; 25 g fat, 1280 kJ), either sweetened (N=10; 14.5 g sucrose) or unsweetened (N=9; 14.5 g Polycose glucose polymer). Forearm blood was sampled pre-meal (0 min), post-meal(+10 min), then +20, +40, +60 and +90 min, and plasma assayed for CCK-8, insulin and C-peptide. Appetite and satiety ratings were taken at intervals up to +120 min. Another group (N=10) ate each version of yoghurt ad libitum on separate days in counterbalanced order.
Sweetness (sucrose) enhanced within-meal appetite ratings, weakened immediate post-meal anticipated satiety, and in the ad-libitum group, increased intake by 48%. Nevertheless, the post-meal increase in plasma CCK-8, insulin and C-peptide did not differ between the isocaloric sweetened and unsweetened yoghurt groups. Participants’ initial judgments of the % fat in the yoghurt were negatively correlated to their rise in C-peptide. Higher restrained eating was associated with less CCK release, but not independently of BMI. Sweetness enhanced intake of a fat-rich food without altering postingestive CCK, insulin or C-peptide release. It remains possible that the cephalic phase release of, or CNS response to, these hormones is altered by sweetness.
EFFECT OF STRESS ON FEEDING BEHAVIOR AND BODY WEIGHT IN RATS . ; Feeding Behavior and Nutrition Research Center, CUSur - Universidad de Guadalajara
Experimental evidence demonstrates that to apply inescapable shock it has an effect on learning, motor activity and social behavior. This procedure is referred as paradigm of "Learned Helplessness" and has been used like a depression model. Inescapable shocks modify ingestion and corporal weight; this could suggest that the paradigm can be very important to study of eating disorders associate with stress and depression (Dess, 1988). The objective of this experiment was to evaluate effects of stress (controllable or uncontrollable) on feeding behavior of albino rats, being used two types of stress: chronic or acute. Eight albino rats were divided in 4 groups. Two groups were introduced in boxes with a water bed (chronic stress) during 24 hours by two days consecutive. The controllable group could start a small surface to dry itself by a time. Both groups of acute stress received 60 shocks (0,6 ma, maxima duration of 10 seconds) in a session of approximately one hour, for two days consecutive. The controllable group could finish to the shock pressing a handle and also finished the shock for rat that did not have control. After this they returned to the same condition of line bases by other five days. During all the experiment registered consumption of water, food and body weight. Results show that stress modified the feeding behavior. The most remarkable effects were registered during chronic stress. The effects persisted during five days after the application of stress.
CONDITIONED SATIETY IN HUMANS REVISITED. . ; Department of Psychology, University of Sussex
According to the concept of learned satiety (LS), associations between the sensory quality and post-ingestive effects of foods may lead to acquired control of meal-size. A previous study (Yeomans et al., 2005 Physiol Behav 86: 487-) could have been interpreted as evidence for LS: participants ate more of a flavoured cereal with lower energy density (ED) after repeated training trials than before, but did not adjust intake of a high ED cereal. Two limitations to that study were addressed here. Firstly, the original fixed serving used in training was larger than voluntary intake, and so may have lead to over-satiation in the high ED condition, and secondly no unflavoured control conditions were run. Here, groups of 12 men were assigned to four conditions based on the trained serving size (150 or 300g) and presence or absence of cues to differentiate high and low ED versions. They consumed the low and high ED versions ad libitum on test days 1,2,7 and 8, and consumed the fixed large or small amounts on training days 3-6, alternating between ED conditions. In the absence of sensory cues between ED versions, mass consumed was the same in high and low ED conditions both before and after training. However, where sensory cues differentiated ED, intake increased post-training in the high ED condition trained with the small load, but decreased in the same condition when a large training volume was used. Changes in flavour pleasantness suggested that acquired liking alone could not account for intake changes. These data provide clear evidence for learned control of meal-size dependent on energy content, adding credence to the LS concept.
CENTRAL CHANGES IN THE SEROTONERGIC SYSTEM IN RESPONSE TO MATERNAL HIGH-FAT DIET IN THE FETAL NONHUMAN PRIMATE. ; ONPRC/OHSU
The central serotonin system (5-HT) has long been associated with weight regulation and obesity, in addition to stress and depression. The 5-HT system modulates feeding behavior through widespread reciprocal innervation of orexigenic and anorexigenic neuropeptide systems. Increased 5-HT activity is associated with hypophagia and weight reduction. Conversely, depletion of 5-HT can cause hyperphagia and obesity. The purpose of these studies was to use our nonhuman primate (NHP) model to investigate the contribution of chronic maternal high-fat diet (HFD) on the fetal central serotonin system. Japanese macaques chronically consumed either: control diet – 13% fat calories or high calorie/fat diet – 35% fat calories. Fetuses were obtained at gestational day 130 (early 3rd trimester) by cesarean section. HFD offspring displayed a dramatic decrease in 5-HT immunoreactive fibers in the arcuate nucleus. In addition, these animals exhibited a reduced mRNA expression of both the 5-HT1B and 5-HT2C receptors and increased expression of 5-HT2A receptors. There was also a significant up-regulation in mRNA expression of the inhibitory 5-HT1A autoreceptor in the dorsal raphe. These changes indicate an overriding suppression of the 5-HT signaling in NHP fetus in response to chronic maternal HFD. The suppression of the 5-HTergic system is likely in response to inflammatory cytokines induced by fetal lipotoxicity. Abnormalities in the development of the 5-HTergic system may impact long-term weight regulation, food preference/palatability, stress responsiveness, as well as energy expenditure.
ARE CHINESE & CENTRAL EUROPEAN STUDENTS ~ TO AMERS IN CONCERNS RE: WT, BODY IMAGE, DIETING & FOOD PREF? BASELINE COMPARISONS FROM CHINA, POLAND & THE US.. ; Univ Mich
Very few populations have escaped the epedemic of obesity. Even China has reported increasing concerns with childhood obesity. This study examined attitudes about body size, dieting, & food preferences in 2 naive samples of male & female college aged students(18-22 yrs) from Beijing and Krakow. Comparisions were made with similar data from US students. Samples: All Ss (approx 300 in each grp) reported ht and wt and wt histories. Body image was tested using the standard male and female figure outlines increasing in size from very thin to normal to obese. Ss rated their ideal body size, their own body size & what they thought the opposite sex would prefer on questionnaires. In addition, attitudes towards dieting were measured. Results: Several Chinese students were moderately overwt while Poland had no overwt students. In particular, Polish students were significantly taller and thinner than the other students and reported eating 'normal' meals including cafeteria and take-out foods. Both sets of students were thinner than US students. Most Polish students were unconcerned about weight and dieting. Still, in both Chin and Poland, female students preferred slightly thinner images and assumed that males. would as well, whereas male students preferred the reverse. Discussion: Lack of exposure to Western diets, more strict school control especially in cafeterias and greater activity (walking, bicycling) are all factors that could contribute to these differences.
Kepensky Institute, Beijing Foreign Language Institute
INCREASED FOOD INTAKE AND ATTENUATION OF CCK-INDUCED INHIBITION OF FOOD INTAKE AND FOS EXPRESSION FOLLOWING SYSTEMIC BLOCKADE OF NR2B/A NMDA SUBUNITS.. ; 1Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, 2Department of VCAPP, College of Veterinary Medicine, Washington State University
Blockade of NMDAR by noncompetitive (MK-801) and competitive (AP5) antagonists increase food intake by acting in the dorsal hindbrain. NMDAR are heteromeric complexes composed of NR1, NR2 and NR3 subunits. Competitive NR2B antagonists potently increase feeding when injected into the hindbrain. NR2 immunoreactivity is present in the hindbrain, vagal afferents and enteric neurons. Thus, NMDA receptors expressed on the endings of vagal afferents in the GI tract could also modulate responsiveness to GI stimuli, and thereby alter food intake. To examine this, we recorded intake of regular chow, palatable nutrient (15% sucrose), and non-nutrient (0.2% saccharin) solutions following various doses of IP administration of D-CPPene (competitive NR2B/A blocker). To determine whether NR2 mediate postoral satiation signals, we tested D-CPPene on CCK-induced feeding and
hindbrain Fos expression. IP D-CPPene (2, 3 mg/kg) produced a significant increase in sucrose and chow intake but not saccharin. Pretreatment with D-CPPene (2 mg/kg) reversed CCK (2µg/kg)-induced inhibition of sucrose intake, and attenuated CCK-induced Fos expression in the DVC. The results show that NMDA NR2 antagonist effects on food intake reflect modulation of GI stimuli and are involved in afferent signal transmission by CCK. Supported by DK-52849 and NS-20561.
DIFFERENTIAL EFFECTS OF CENTRAL OR INTRA NUCLEUS ACCUMBENS SHELL MCHR1 SIGNALLING ON FOOD INTAKE AND ENERGY EXPENDITURE, ASSESSED BY INDIRECT CALORIMETRY. ; Hôpital Laval
The central melanin-concentrating hormone (MCH) system is a major determinant of body metabolism. Particularly, MCH projection toward nucleus Accumbens shell (NAcSh) have been proposed to be part of a hypothalamic-limbic circuit which could insure the cross-talk between the ‘homeostatic’ and ‘non-homeostatic’ regulations of energy balance. However, to date, the specificity of intra NAcSh MCHR1 signalling among the wide range actions currently attributed to the central MCH system, such as its effect on energy expenditure, has not been investigated. We thus implemented parallel protocols with intra NAcSh or ICV injections of a potent MCHR1 agonist. The evolution of total energy expenditure and substrate oxidations following the injections was assessed in vivo trough indirect calorimetry recordings. Food intake following the injections was measured as well. In order to evaluate the changes in thermogenesis independently of the meal size and its thermogenic response, it was necessary to consider a situation where rats were pair fed with controls. Results indicate that MCHR1 signalling in the NAcSh might account for a large part of the orexigenic effect of central MCH system, without being implicated in its other effects on energy expenditure like decreased lipid oxidations. This delineates more clearly the specificity of MCH actions in the Nucleus Accumbens and finally, constitutes a first step towards a better understanding of this important link between hypothalamus and limbic system.
COCAINE- AND AMPHETAMINE-REGULATED TRANSCRIPT (CART) PEPTIDE IMMUNOREACTIVITY IN THE BRAIN OF THE OBESE OLETF RAT.. ; 1Dept. Neural & Behav. Sci., Penn State Univ., 2Dept. Nutritional Sci., Penn State Univ., 3Central Electron Microscopic Lab., Univ. of Pecs
Cocaine- and amphetamine regulated transcript (CART) peptide
is expressed in brain areas that play a role in homeostatic regulation and
reward. CART has been shown to reduce food intake in rodents but the underlying
mechanisms and the relevance of this effect to obesity yet remain unknown.
Therefore, the present study investigated CART peptide immunoreactivity (CARTir)
in various brain regions of adult (35-40 wks) Otsuka Long Evans Tokushima Fatty
(OLETF) rats. The OLETF rat is a null-mutant to the CCK-1 receptor, and used as
a model for dietary obesity due to its chronic hyperphagia, and increased
avidity for palatable foods. Whereas the distribution of CARTir neurons and
axonal networks was identical in OLETF and age-matched lean LETO rats,
intensity of CARTir was significantly reduced in the rostral part of the
nucleus accumbens (p<0.01), the basolateral complex of the amygdala
(p<0.02), and the rostro-medial nucleus of solitary tract (p<0.001) of
the OLETF rats. These areas are involved in reward and integration of taste and
viscerosensory information and have been previously associated with altered
functions in this strain. The findings suggest that in addition to previously
described deficits in peripheral satiety signals and augmented orexigenic regulation
in the hypothalamus, the anorectic effect of CART may also be diminished in
OLETF rats. Supported by NIH DK065709, and Hungarian State
Eötvös Scholarship to H.A..
REGULATION OF FOOD INTAKE AND ANXIETY BY &ALPHA;-MSH REACTIVE AUTOANTIBODIES. ; 1Appareil Digestif Environnement Nutrition Laboratory (ADEN EA3234), 2Experimental Neuropsychopharmacology Laboratory (CNRS FRE 2735), 3Immunopathology Laboratory (Inserm U519), Biomedical Research Institute Rouen University & Hospital & IFR23, 4Department of Neuroscience, Karolinska Institutet
α-Melanocyte-stimulating hormone (α-MSH) is a neuropeptide critically involved in regulation of energy and emotional homeostasis. Autoantibodies (autoAbs) reactive with α-MSH have been recently identified in human subjects while their levels correlated with psychological traits in patients with eating disorders. So far it was unknown if these autoAbs are involved in the regulation of feeding and anxiety and if their production can be influenced by stress. In the present work, we found that α-MSH reactive autoAbs are present in rat blood and that repeated exposure to mild stress increase their levels and affinity and that this change is associated with modifications in feeding and anxiety during exposure to strong stress such as food restriction. Using passive transfer, we show that high affinity α-MSH autoAbs from rats exposed to repeated mild stress are able to suppress food intake and anxiety and modify the gene expression of hypothalamic neuropeptides involved in the regulation of appetite in naïve rats. These data provide the first evidence that α-MSH autoAbs are involved in regulation of feeding and mood, assigning a new role for the immune system in the control of motivated behavior and stress-response.
METHOTREXATE-INDUCED ANOREXIA IS ASSOCIATED WITH ALTERATION OF HYPOTHALAMIC NEUROPEPTIDE EXPRESSION AND PLASMA LEVELS OF &ALPHA;-MSH REACTIVE AUTOANTIBODIES. ; 1ADEN (Appareil Digestif Environnement Nutrition) Laboratory, Faculty of Medecine-Pharmacy, IFR23 & Rouen University Hospital, 2Nutrition Department, Nestlé Research Center
Anorexia and enterocolitis are side effects caused by a cancer chemotherapeutic methotrexate (MTX). To investigate putative mechanisms of MTX-induced anorexia, Sprague Dawley male rats received MTX (2.5 mg/kg s.c. for 3 days), while pair-fed and ad libitum-fed control rats received saline. Rats were fed with powdered standard chaw and their food intake and body weight were monitored in individual metabolic cages. Rats were killed on days 5 or 19 after first injection of MTX. Day 5 in MTX-treated rats was characterized by maximal suppression of food intake and body weight and presence of inflammation in colonic mucosa. On day 19 no signs of intestinal inflammation were found in MTX-treated rats but they still exhibited significantly lower body weight vs. control rats. In pair-fed rats, the levels of hypothalamic NPY mRNA were increased (p<0.05) while levels of POMC mRNA were decreased (p<0.05) on day 5, providing the evidence of a negative energy balance. However, in MTX-treated rats no significant changes of NPY or POMC mRNA were found at day 5 suggesting that acute anorexia following MTX treatment may be related to altered expression of hypothalamic neuropeptides triggered by intestinal inflammation. The levels of free α-MSH reactive autoAbs were decreased at day 5 (p<0.05), but increased at day 19 (p<0.05) in MTX-treated rats suggesting that in the absence of intestinal inflammation α-MSH reactive autoantibodies can be involved in wasting syndrome persisting after MTX treatment.
EXERCISE MODIFIES BODY WEIGHT SET-POINT IN DIET-INDUCED OBESITY PRONE RATS . ; In Vivo Pharmacology, Rheoscience AS
Background Exercise has been suggested to prevent onset of obesity in juvenile obesity-prone rats probably by effecting the development of the neural circuits controlling obesity. Materials and Methods: Young diet-induced obesity prone (DIO) rats were placed in a running wheel cage immediately following weaning and allowed to exercise (voluntary) during a two week training period. Based on the training activity we then divided the rats into runners and non-runners. Non-runners were placed in a standard cage as a sedentary reference, while runners were stratified into 3 groups: i) wheel access for additional 11 weeks, ii) wheel access for additional 6 weeks followed by 5 weeks of blocked wheels, iii) 11 weeks of blocked wheels. Results: We demonstrate that young DIO rats which was exercised (voluntary) for 8 weeks followed by a forced sedentary period of 5 weeks, displayed a similar body weight gain pattern, body composition, insulin sensitivity, and plasma lipid profile as rats exercising through the entire intervention period of 13 weeks. Conclusion: Our data suggests that exercise in young obesity prone rats may protect against the development of obesity.
FUNCTION AND CELLULAR SIGNALING OF BITTER TASTE RECEPTOR AGONISTS IN THE MAMMAL GUT . ; 1Department of Anatomy, Physiology, & Cell Biology, University of California, 2Department of Neuroscience, University of Pittsburgh, 3CURE Digestive Diseases Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California
Receptors for bitter taste, the T2R
family and the a subunit
of the taste-specific G-protein, gustducin (Gagust), are expressed in the gastrointestinal (GI) mucosa. Intragastric administration of T2R agonists activates neurons in the brain stem via a vagal, CCK1 and Y2
receptor pathway (Hao et al AJP Reg 294:R33, 2008). Further studies
were performed to understand the molecular signaling pathways and functional role of T2R
expression in the gut. A mixture of T2R
agonists (denatonium benzoate DB 10 mM, phenylthiocarbamide PTC 10 mM,
6-propyl-2-thiouracil 5 mM, quinine 5 mM and D-[-]salicin 5 mM) or single
agonists (DB or PTC) were administered intragastrically (IG) to either mice
(0.1 ml) or rats (1 ml). T2R agonists induced an increase in pCaMKII expression in
duodenal CCK endocrine cells (p<0.005) and 5-HT-expressing cells (p<0.01)
and increases pCaMKII expression in the nodose ganglion (p<0.05). In rats, intragastric administration of theT2R agonist mixture induced a robust conditioned flavor avoidance (CFA, p<0.001) and activated neurons in the nucleus of the solitary tract, ventrolateral medulla, lateral parabrachial nucleus and central amygdala. In mice, intragastric PTC but not DB inhibited food intake (p<0.001) and induced CFA (p<0.001). Conclusion: T2R agonists activate endocrine cells in the gut wall, nodose ganglion and central neurons. These data suggest that T2R agonists may regulate CFA and food intake via vagal pathway.
ENDOCRINE AND HYPOTHALAMIC RESPONSES TO CHRONIC FOOD RESTRICTION AND WEIGHT RESTORATION IN THE RAT . ; Dept. of Psychological Sciences, Ingestive Behavior Research Center, Purdue University
Chronic food restriction induces alterations in endocrine responses to ingestion of a meal in human subjects, some of which persist with weight restoration. These studies characterize how chronic food restriction and body weight (BW) restoration affects hormonal responses to a meal in the rat. Endocrine responses to ingestion of a meal (Ensure) were measured after rats (CR) were calorie-restricted (70% of controls), and then partially (PR), and fully (FR) weight restored. Compared to controls, CR, PR, and FR rats exhibited decreased pre-prandial plasma ghrelin levels (5456.1±994.2 [Control], 1661.7±263.1 [CR], 2124.3±296.1 [PR], 2726.8±644.9 [FR] pg/ml). Only controls exhibited a decrease in plasma ghrelin 15 minutes after the meal onset (1167.5±197.3 [Control], 1397.1±109.4 [CR], 2104.1±369.8 [PR], 3148±584.0 [FR] pg/ml). In a second group, endocrine profiles and hypothalamic gene expression levels were assessed before, during and after weight restoration after chronic caloric restriction. Hypothalamic mRNA expression levels (proopiomelanocortin (POMC), agouti-related protein (AgRP), and neuropeptide Y (NPY)) were measured in CR, PR and FR rats before and 2h after feeding. Compared to controls, POMC expression was significantly decreased in CR rats, and AgRP expression was decreased across all restricted groups prior to feeding, and increased in PR and FR groups following food access. These data suggest persistent changes across multiple axes following chronic food restriction in rats.
HIGH FAT FEEDING AFFECTS EATING PATTERNS IN OBESITY PRONE AND RESISTANT ANIMALS. ; 1School of Dietetics and Human Nutrition, McGill University, 2McGill Nutrition and Food Science Centre, Royal Victoria Hospital
Irregular meal size and number are reported in dietary-induced obese animals. We examined these behaviours using one-minute data from Diet ScanR methodology, in adult Sprague-Dawley rats fed a high fat diet (canola oil or butter) (n=20) and in a control group fed chow (n=10) for 50 days. Based on their obesity index at week 4, rats were categorized as obesity prone or resistant. Feeding rhythms were assessed at week 6 for 7 days; meal size, frequency and intermeal intervals were calculated. The highest rates of weight gain were in butter fed prone rats. All the animals had more frequent meals at night, but nocturnal and diurnal meal sizes of the high fat fed animals were comparable. Butter feeding resulted in less frequent meals (P=0.01) and longer intermeal intervals than feeding canola (P=0.006) during the day. Meal numbers were different among the phenotypes: control>resistant>prone at night (P=0.0001) and control>resistant/prone during the day (P=0.002). Meal size of the butter fed prone animals was larger than the others, while in butter fed resistant animals it was comparable to the canola and controls. In conclusion, high fat feeding results in an increase in diurnal meal size and a decrease in meal number in both phenotypes, albeit more so in animals prone to obesity. Our data suggest that irregularity in meal patterns is more (or at least partly) related to feeding high fat diets than obesity per se. These findings support the use of low fat diets in weight reduction programs.
ANTAGONISM OF CORTICOTROPIN RELEASING FACTOR RECEPTOR 1 (CRFR1) PREVENTS SUSTAINED WEIGHT LOSS IN RATS EXPOSED TO REPEATED RESTRAINT STRESS. . ; University of Georgia
Rats exposed to 3 hours of restraint stress on each of 3 days (RRS) lose weight and do not return to control weight after restraint has ended. To test the importance of CRFR1 in mediating this response 36 ad libitum-fed male Sprague Dawley rats were divided into four weight-matched groups after 5 baseline days. Two groups were RRS and two were controls. Ten minutes before each restraint the rats were injected i.p. with 20 mg/kg antalarmin in 10% DMSO, 90% PBS (RRS/ANT, Control/ANT) or vehicle (RRS/Veh, Control/Veh). All RRS rats ate less than Controls and lost weight on the days of restraint, but the effect was exaggerated in RRS/ANT rats. RRS/Veh rats weighed less than Control/Veh rats throughout the experimental period. RRS/ANT rats returned to the weight of Control/ANT rats 18 days after the end of RRS. Corticosterone release during restraint was not different between Controls or between RRS rats, but baseline corticosterone was increased in all ANT rats. Twenty six days after RRS all rats were exposed to the mild stress (MS) of housing on wet bedding for 2 hours. Corticosterone was higher in both groups of RRS rats compared to Controls 45 min after the start of MS. Thus, activation of CRFR1 is required for the sustained reduction of body weight in RRS rats, but a different pathway is responsible for the exaggerated adrenal response to novel stress in the post-RRS period. Because CRFR2 are responsible for stress-induced hypophagia these results suggest that CRFR1 inhibit activity of CRFR2 during stress. Supported by NIMH MH06828101
CONTRIBUTION OF HINDBRAIN GLP-1 RECEPTOR ACTIVATION TO FEEDING CONTROL &NDASH; ROLE OF ENDOGENOUS GLP-1 AND OF ERK / AMP-KINASE PATHWAYS. ; UPenn
Central GLP-1R activation inhibits food intake. It remains unclear: 1) if endogenous central GLP-1R activity contributes to intake control; 2) what intracellular signaling pathways mediate suppression of intake by central GLP-1R activation. Given that NTS neurons are the endogenous central source of proglucagon and that caudal brainstem processing is sufficient to mediate suppression of intake by 4th icv GLP-1R agonist Exendin-4 (Ex-4), we examined the role of endogenous hindbrain GLP-1R to intake control. GLP-1R antagonist (Ex-9; 10µg, 4th icv) delivered to 16h food deprived rats following preload (Ensure), increased intake at 0.5, 1.0, 1.5 & 24h by 31, 35, 23, & 10% compared to control. Intracellular signaling pathways mediating intake inhibitory effects of hindbrain GLP-1R agonist were examined by 4th icv pre-treatment with: 1) mitogen-activated ERK inhibitor, UO126 (2µg), 2) or in separate trials, a AMPK activity promoter, AICA (0.3mg) delivered at dark onset. UO126 attenuated (8.5±0.9g) Ex-4 (0.2µg) intake suppression (5.8±0.9g vs 9.7±1.3g: Ex-4 & vehicle). The intake suppressive effect of Ex-4 (0.1µg; measured in feedometers ±0.1g/m for 24h) began 7h-post inj & reached a max sustained suppression of ~10g at 12h (lights on)-post inj. Increasing hindbrain AMPK activity by AICA attenuated Ex-4’s satiating effect by ~50%. Conclusion: 1) endogenous hindbrain GLP-1R activation contributes to ntake control and 2) ERK and AMP-kinase pathways contribute to the feeding effect of hindbrain GLP-1R agonist. DK21397 & -077484.
NEUROPEPTIDES AS SIGNALING AGENTS IN THE MAMMALIAN TASTE BUD.. ; College of Dentistry, The Ohio State University
The evolving view of the taste bud increasingly suggests that it operates as a complex signal processing unit. A number of neurotransmitters and their corresponding receptors are now known to be expressed in subsets taste receptor cells (TRCs) of the mammalian bud. These expression patterns set up hard-wired cell-to-cell communication pathways whose exact physiological roles still remain obscure. Additionally, neuropeptides and their receptors are also expressed in TRCs. It is likely neuropeptides are co-expressed with neurotransmitters and function as neuromodulators. Four neuropeptides have been identified in TRCs: cholecystokinin (CCK), neuropeptide Y (NPY), vasoactive intestinal peptide, and somatostatin. Of these, CCK and NPY are the best studied. These two peptides are co-expressed in the same presynaptic cells; however, their postsynaptic actions are both divergent and antagonistic. CCK and its receptor, the CCK-A subtype, are expressed in the same subset of TRCs. Activation of these cells produces a number of excitatory physiological actions. On the other hand, NPY and its receptor, the NPY-1 subtype, are expressed in different cells and NPY produces inhibitory actions. CCK-A expressing TRCs are bitter-sensitive cells whereas co-expression of the NPY-1 receptor with T1R3 suggests these TRCs may be sweet-sensitive. Thus these two peptides may be working in concert during bitter stimulation to both modulate the excitation of bitter-sensitive TRCs while concurrently inhibiting sweet-sensitive cells. This modulatory process is similar to the phenomenon of lateral inhibition that occurs in other sensory systems.
OSMOTIC STIMULATION OF SFO CAUSES CFOS EXPRESSION IN PVN IN CONSCIOUS RATS.. ; Department of Psychology, University of Washington
Both the subfornical organ (SFO) and paraventricular nucleus of the hypothalamus (PVN) contain osmoreptors, but the osmoreceptors in circumventricular organs, such as SFO, appear to be the principal stimuli for drinking and vasopressin secretion. Surprisingly, no published studies have demonstrated that an infusion of hyperosmotic fluid locally into a CVO causes drinking, vasopressin secretion, or activation of neurons in related hypothalamic areas in conscious animals. Five male Long-Evans rats with SFO-targeted cannulas were screened for drinking in response to angiotensin (ANG II). Two days later, all rats received a sustained intracerebral infusion of 1 M artificial CSF with the extra osmoles as NaCl. The rate of infusion was 0.8 µl/h for 90 min. Drinking latencies were recorded, but no rat was allowed to drink more than a few licks. The brains were prepared for analysis of cFos expression by immunohistochemistry. Two of the 5 rats had cannulas situated in the SFO, and these animals drank 7 and 12 ml in 30 min in the ANG II test and had the shortest drinking latencies during the hyperosmotic infusion. The other 3 rats had cannulas situated <1 mm rostral to the SFO in the septum, did not drink to ANG II, and had long latencies to drink during the infusion. Hyperosmotic infusions into the SFO caused cFos expression in the supraoptic nucleus and PVN (p = .03), but septal infusions did not. Neither infusion site caused cFos expression in the OVLT, which might have been expected if the hyperosmotic signal had been communicated to the hypothalamus through the CSF instead of through neural pathways. The data support a role for the SFO as an osmoreceptive area that causes drinking and cFos expression in the hypothalamus in response to hyperosmolality.
PLASMA LEPTIN, INSULIN AND GHRELIN CONCENTRATIONS REFLECT NUTRITIONAL STATUS, NOT ADIPOSITY, IN RATS RECOVERING FROM FORCED UNDERWEIGHT. . ; Physiology and Behaviour Group, ETH Zurich
We explored the endocrine mechanisms mediating compensatory eating following forced weight loss, a phenomenon often cited in support of the hypothesis that the regulation of energy homeostasis results in constant body adiposity. In order to better disentangle the effects of adiposity per se from acute nutritional status, we used methods not commonly applied in this context.
Male LE rats with jugular vein catheters were fed ad libitum (AL) or restricted to 60% of baseline intake, with the daily ration offered in 6 meals/d, until they reached 80% of the weight of age-matched AL (= underweight groups, UW). UW were then either returned to AL feeding (= UW-AL) or were yoke-fed to AL (=UW-Y) for 1 done day and sacrificed (1 h before dark onset after a 3-h fast).
UW-ALs ate 15% more on the re-feeding day than AL. Body adiposity (estimated as epididymal + retroperitoneal fat weights) was reduced ~40% in UW, with no difference between UW-AL and UW-Y. Plasma leptin and insulin levels were reduced in UW, and ghrelin was increased. Hormone data in UW-AL and UW-Y were similar and combined; 1 d of re-feeding significantly increased plasma leptin and insulin levels and decreased ghrelin, so that the level of each hormone was indistinguishable from AL; i.e., 1 d of feeding at 100-115% of the AL level reversed plasma hormone levels despite continuing markedly reduced body adiposity.
These data are inconsistent with the hypotheses that leptin, insulin, and ghrelin are “adiposity signals" whose levels drive weight-regulatory eating.
EFFECTS OF ALPHA-LACTALBUMIN-, GELATIN WITH OR WITHOUT ADDED TRYPTOPHAN-PROTEIN BREAKFASTS ON HUNGER, 'SATIETY' HORMONES, AND PROTEIN KINETICS. ; 1Maastricht University, 2Top Institute Food and Nutrition
Tryptophan(TRP) may contribute to the satiating effect of proteins.
We compared 3 breakfasts, with either alpha-lactalbumin(a-lac,high TRP), gelatin(low TRP) or gelatin with added TRP(gel+TRP,high TRP) as the protein source, on appetite and energy intake.
24 healthy subjects(22-29kg/m2;19-37yr) received a standardized custard (20% of daily energy need) at t=0 with 10/55/35En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite, GLP-I, ghrelin, and amino acid(AA) plasma concentrations, and energy intake during a subsequent ad libitum lunch were determined.
At t=240min hunger-suppression was stronger in the breakfast with a-lac compared to gel(+TRP).
Total AA-concentrations(sumAA) were lower with a-lac compared to gel(+TRP) from t=180 to t=240min. Until t=100min, TRP concentrations were higher in a-lac compared to gel(+TRP). From t=100 to t=240min, TRP concentrations were similar with a-lac vs gel+TRP, but higher compared to gelatin. TRP/LNAA plasma ratio was lower at t=100min for gel+TRP compared to a-lac and gelatin. GLP-I and ghrelin concentrations were similar for the 3 diets. SumAA, TRP, TRP/LNAA, GLP-I and ghrelin concentrations were not correlated to hunger. Energy intake during lunch was similar for all 3 diets.
Summarized, an a-lac breakfast suppresses hunger more than a gel(+TRP) breakfast. This cannot be explained by effects on sumAA, TRP, TRP/LNAA, GLP-I and ghrelin. The effect was insufficient to affect energy intake.
THE NUCLEUS ACCUMBENS AS INTEGRATOR OF FEEDING AND SATIETY INFORMATION IN THE CONTROL OF MOTIVATION TO EAT . ; 1Princeton University, 2Rockefeller University, 3Universtiy of Los Andes
The nucleus accumbens integrates “Go” and “Stop” information from the hindbrain, hypothalamus, medial prefrontal cortex, hippocampus, thalamus and amygdala. This is depicted as a final common pathway through which feeding and satiety factors are integrated in the control of motivation. "Decisions" are expressed in terms of the relative activity in NAc outputs, one for motivation to eat and one for avoiding food. We propose that dopamine (DA) and acetylcholine (ACh) in the NAc have opposing roles in modulating these two major output systems. New studies with muscarinic agonists and antagonists (arecholine and pirenzepine) suggest that M1-type ACh receptors inhibit the approach pathway, while M2-type receptors stimulate the avoidance pathway. DA has the opposite effect. In behavioral terms, DA release fosters a meal, and ACh release causes meal satiation, or in the case of sickness, a conditioned taste aversion. When DA release is excessive and repeated, an opponent process develops as a compensatory mechanism. The opposing role of ACh is revealed during withdrawal when DA levels decrease dramatically, and the animal enters an ACh-mediated state of anxiety or behavioral depression. This can occur after a period of drug abuse or sugar bingeing. "Self-medication" with drug or food may correct the sense of well-being and DA/ACh imbalance.
Supported by USPHS grants DA10608 (B. G. Hoebel) and MH 65024 (B.T. Walsh).
THE EFFECT OF VISCOSITY ON LEARNED SATIATION. ; 1Top Institute Food and Nutrition, 2Division of Human Nutrition, Wageningen University, 3TNO Quality of Life
Oral processing time affects the sensory exposure to foods and thus may influence the conditioning process of learned satiation. In the current conditioning experiment we studied 2 foods with different oral processing time: a liquid and a semi-solid yogurt.
Forty-six healthy subjects (22±2y) consumed for breakfast ad libitum a novel flavored high energy density (HED) yogurt (150 kcal/100g) or low energy density (LED) yogurt (50 kcal/100g), with 10 exposures to each yogurt on alternate days. Twenty-four subjects received a liquid yogurt and 22 a semi-solid yoghurt. Preliminary analyses showed that at baseline subjects consumed more of the liquid product, regardless of energy density (liquid: 516±214g; semi-liquid: 457±250; p<0.05). In the liquid group, no significant modifying effect of energy density on ad libitum consumption over the 10 exposures was observed (p=0.45). However, in the semi-liquid group a modifying effect of energy density was observed (p<0.05); consumption over the 10 exposures declined for the HED yogurt (-50±19g;p<0.05) but not for the LED yogurt (3±23g;p=0.89). These results suggest that a higher oral processing time and sensory exposure facilitates the conditioning process of learned satiation. Further data-analyses are currently performed.
THE EFFECT OF VISCOSITY ON LEARNED SATIATION. ; 1Top Institute Food and Nutrition, 2Division of Human Nutrition, Wageningen University, 3TNO Quality of Life
Oral processing time affects the sensory exposure to foods and thus may influence the conditioning process of learned satiation. In the current conditioning experiment we studied 2 foods with different oral processing time: a liquid and a semi-solid yogurt.
Forty-six healthy subjects (22±2y) consumed for breakfast ad libitum a novel flavored high energy density (HED) yogurt (150 kcal/100g) or low energy density (LED) yogurt (50 kcal/100g), with 10 exposures to each yogurt on alternate days. Twenty-four subjects received a liquid yogurt and 22 a semi-solid yoghurt. Preliminary analyses showed that at baseline subjects consumed more of the liquid product, regardless of energy density (liquid: 516±214g; semi-liquid: 457±250; p<0.05). In the liquid group, no significant modifying effect of energy density on ad libitum consumption over the 10 exposures was observed (p=0.45). However, in the semi-liquid group a modifying effect of energy density was observed (p<0.05); consumption over the 10 exposures declined for the HED yogurt (-50±19g;p<0.05) but not for the LED yogurt (3±23g;p=0.89). These results suggest that a higher oral processing time and sensory exposure facilitates the conditioning process of learned satiation. Further data-analyses are currently performed.
CUE-POTENTIATED FEEDING. ; Johns Hopkins University
Decisions about when and what to eat are critical to survival. Associative learning processes complement regulatory mechanisms in the control of eating by providing opportunities for the anticipation of upcoming needs. Environmental cues associated with the availability and scarcity of particular foodstuffs can dramatically alter consumption of those foods. Although the alterations in feeding produced by such cues are typically adaptive, they may also contribute to pathological consumption patterns. I will discuss behavioral and circuit analysis studies of information processing involved in initiating and maintaining ingestive behavior, with an emphasis on cases in which neural signals provided by extrinsic feeding-related cues conflict with concurrent regulatory and hedonic signals.
EFFECTS OF EXPERIMENTAL SPINAL CORD INJURY ON FOOD INTAKE, BODY COMPOSITION AND GASTROINTESTINAL EXPRESSION OF CD36 MRNA IN RATS.. ; Pennington Biomedical Research Center
Failure to maintain body weight within prescribed ranges often occurs in humans with spinal cord injury (SCI). This population is also at risk for increased fat mass below the lesion. In rats with high (spinal T3) or low (spinal T9) SCI, we sought to identify short-term derangements in feeding, body weight and fat mass. We also assayed gastrointestinal (GI) mRNA levels of the CD36 lipid transporter to begin to address diminished GI absorptive capacity. Daily body weight and mean energy intake (MEI) of low fat diet (28% protein, 13% fat, 59% carbohydrate) was collected for 3w after SCI or sham surgery (n=26). Body weight and MEI after sham surgery was significantly lower than preoperative baseline for only the first 24hrs after surgery. Both T3 and T9 SCI suppressed postoperative body weight below baseline for 14d and 12d (respectively) while MEI remained below baseline for 7d and 4d (respectively). Animals with T9 SCI had significantly lower percentage of total fat pad weights (epididymal + retroperitoneal) than shams at 7d post-SCI. Compared to shams, total fat pad weights were significantly lower in both 21d T3 and T9 injured rats despite a significantly greater MEI. However, NMR analysis of the percentage of whole body fat mass was not significantly different. GI expression of CD36 mRNA was similar across 7d survival groups, but was doubled in 21d T3 SCI rats. This suggests that: 1) body composition changes occur rapidly after SCI; 2) fat mass may redistribute through other tissues; and 3) high thoracic SCI might alter nutrient absorption in the GI tract.
IMPAIRED GASTRIC EMPTYING USING THE 13C-OCTANOIC BREATH TEST IN RATS WITH EXPERIMENTAL SPINAL CORD INJURY.. ; Pennington Biomedical Research Center
Patients with spinal cord injuries (SCI) most often present reduced gastric emptying as well as a risk of reflux and aspiration of gastric contents. In an animal model of high thoracic SCI, gastric motility and reflex-evoked gastric relaxation is diminished 3d post-injury. We tested the post-SCI changes in gastric emptying using the 13C-octanoic breath test at 3, 7, 21 and 42d in rats that received either a control surgery without SCI, high (spinal T3) or low (spinal T9) SCI. Rats fasted 16h were placed in closed chambers and fed a 1g meal doped with 50 ug of 13C-octanoic acid. Compared to surgical controls (n=7), animals with complete T3 SCI (n=6) or T9 SCI (n=7) had significantly less percent recovery of 13C substrate (86.6±6.7% vs. 37.4±4.1% or 48.5±6.5%, respectively, p<0.05) at 3d. The peak recovery time (tlag) was significantly different (84.5±4.7 vs. 52.5±4.3 or 69.8±6.6 min, respectively, p<0.05). Furthermore, half-emptying time (t1/2) was significantly shorter (129.7±7.3 vs. 68.2±5.8 or 93.1±8.2 min, respectively, p<0.05). This paradoxical acceleration of t1/2 may have been due to the 13C substrate that remained unaccounted for at the termination of the 6 hr test. Differences in 13C percent recovery, tlag and t1/2 were all significant from surgical control at 7d and 21d but not 42d. These data demonstrate that gastric reflex function remains impaired at least 3w after SCI. This dysfunction includes reduced levels of vagally-dominated gastric motility and, possibility, gastric retention combined with pyloric sphincter dysfunction. The post-SCI suppression of these vago-vagal gastric reflexes suggests that SCI may interrupt ascending spinal afferent input to brainstem vagal nuclei. Support: NINDS #49177
MODULATION OF THE VOMITING RESPONSE IN HOUSE MUSK SHREWS BY FOOD RESTRICTION. . ; 1Monell Chemical Senses Center, 2University of Pennsylvania
Evidence suggests a significant interaction between neural circuits for feeding and emesis. For example, appetite stimulants, such as ghrelin and endocannabinoids, have been shown to be anti-emetic. Here we tested the hypothesis that stimulation of “hunger” would increase the emetic threshold by assessing the effects of food restriction on emetic responses to nicotine in the house musk shrew. Unlike rodents, the shrew possesses a vomiting response and nicotine (2 mg/kg, sc) was determined to produce a consistent sub-maximal emetic response. 24 h, but not 3 h, of food restriction significantly increased food intake for 1 h upon refeeding. Furthermore, both 24 and 3 h of food restriction were sufficient to empty the gut of food but did not change % body fat. 24 h food-deprived animals showed fewer emetic responses (1.9 ± 0.8) than animals deprived for 3 h (6.6 ± 1.3). These results indicate that mild food restriction can significantly reduce emetic responses and highlights the close association between gut-brain systems controlling food intake and emesis. In a broader context, it might prove important to understand these interactions in order to control anorexia, emesis, and nausea in chronic diseases, such as late stage cancer.
This work was supported by NIH grant DK065971.
VISFATIN EXPRESSION IN BROWN ADIPOSE TISSUE OF C57BL/6J MICE. ; 1A.I.Virtanen Institue, 2Poznan Uviv. of Medical Sciences, 3Inst. of Biomedicine
Visfatin is a novel member of the adipokine family and is identical to nicotinamide phosphoribosyltransferase (Nampt), an essential rate-limiting enzyme in biosynthesis of nicotinamide adenine dinucleotide (NAD+). Regulation of visfatin expression remains
largely unknown. To study the regulation of visfatin in response to nutritional
state, we examined expression levels of visfatin mRNA in fasted and fed mice.
3-month-old male C57BL/6J mice were fed ad libitum, or fasted 18 hrs and sacrificed. The mRNA expression was analyzed by real-time PCR. Protein levels were assessed by Western blotting.
Visfatin mRNA in brown adipose tissue (BAT) was 10-fold higher compared to liver (p≤
0.001) and 2,5-fold higher than in visceral WAT. Visfatin mRNA was 2-fold higher in visceral than in subcutaneous WAT. The expression of visfatin in BAT was confirmed on protein level (4,8-fold higher compared to liver, p≤0,01 ). Visfatin mRNA in BAT and liver was significantly increased by 2-fold and 1,6 fold (p≤0,01 in both), respectively, after 18 hrs fasting, while mRNA in visceral or sc WAT did not change compared to fed mice.
Visfatin is highly expressed in brown adipose tissue in mRNA and protein levels and visfatin mRNA is upregulated in liver and BAT by fasting. As visfatin is a regulator of NAD+ synthesis and NAD+ substrate for sirtuins- regulators of response to caloric restriction, the expression of visfatin in BAT might suggest a novel role of visfatin in the regulation of energy metabolism and thermogenesis.
INSULIN DIFFERENTLY MODULATES HYPOTHALAMIC MITOCHONDRIAL ENERGY METABOLISM IN FED OR FASTED MICE. INVOLVEMENT IN FOOD INTAKE REGULATION?. ; UMR 5241 CNRS-Paul Sabatier University IFR109
In hypothalamus, mitochondria have been demonstrated to be involved in nutrients sensing but little is known concerning a mitochondrial insulin effect. The aim of our study was thus to determine, in mice, whether i) insulin may modulate mitochondrial functions and ii) this effect varies according to metabolic state. O2 consumption, measured by oxygraphy in fresh hypothalamus explants was similar in fed and fasted mice on glutamate whereas it was lower in fasted mice on succinate. Whatever the metabolic state of the mice, insulin (3 nM) increased O2 consumption with glutamate. By contrast, insulin increased O2 consumption with succinate only in fasted mice. This increase allows to restore O2 consumption which was observed in fed mice in basal condition thus suggesting that insulin might improve free fatty acids utilisation in fasted mice. In in vivo experiments, third ventricular insulin injection strongly inhibits food intake, in fed mice, as already described. However, this effect was not observed with similar insulin concentration (3 nM) in fasted mice. Experiments are currently under investigation in order to assess insulin effect on mitochondrial products and to establish a link between the level of these products and food intake regulation. Altogether these data demonstrate that the effects of insulin on mitochondrial function in hypothalamus and on food intake vary according to the metabolic state.
IS THERE NEGATIVE REINFORCEMENT OF EATING BY ENERGY-FLOW DEFICIT IN HUMAN BEINGS?. ; 1Dietetics & Human Nutrition, McGill University, 2Psychology, University of Birmingham
Rats learn to eat more of a test food that cues a longer duration of food deprivation. This anticipatory eating is negatively reinforced by flow of energy out of lean tissues, which is countered by the extra intake. Such instrumental control of eating has yet to be tested in humans. Increased intake in expectation of delayed subsequent eating has to be excluded, even though human conditioning may require awareness of the stimulus-reinforcement contingency. Our plan is that volunteers be given two meals a day on non-consecutive days. In pseudo-random sequence, two distinctive breakfast menus are followed by a buffet “satiety test” around either lunchtime or suppertime. Participants are asked not to eat after their evening meal the previous day and to eat normally after the buffet. The time of the buffet for that day is given to participants once they finish the breakfast. Anticipatory eating would increase the size of the breakfast that had preceded the longer delay, relative to the breakfast before the shorter delay; in rats, the extra eating reduces effects of deprivation and so declines, which in turn induces relearning. At the end of the experiment, each participant writes freely what they think the research team’s hypotheses were and then rates the likelihoods of a wide range of hypotheses, including that one of the two types of breakfast precedes omission of lunch. These measures of contingency awareness will be related to the changes in amounts eaten of the two breakfasts, to test for learnt intake without expectation.
A RODENT MODEL OF THE ADJUSTABLE GASTRIC BAND - MECHANISMS OF ACTION. . ; 1Monash University, 2Monash University
surgery has become an important component of the complete arsenal of anti
obesity therapies. Of the possible surgical approaches, adjustable gastric
banding (AGB) is gaining rapid acceptance; however, the mechanisms that
underlie its impact on satiety remain very poorly defined.
The aim of the present study is to
develop a rodent model of the AGB and define the way in which sensory afferents
arising from the stomach interact with central centres known to be crucial to
long term energy balance.
A band with an inflatable cuff
operated via an externalised port has been developed that when fitted to the
gastro oesophageal junction can be adjusted incrementally to cause staged reduction
of food intake and weight loss over several weeks. The sensory neural pathways
that may mediate this effect were investigated using a modified herpes simplex
virus (HSV129) which is transported transynaptically into CNS circuitry
following injection into the stomach wall underlying the band.
Virally labelled neurons were found
in the lateral and dorsal hypothalamus, arcuate nucleus and in the cerebral
cortex where they were colocalised with feeding related peptides including
orexin A and melanin concentrating hormone.
These data show for the first time
the possibility that the AGB, at least in the rodent model, may exert its
affects via sensory pathways directed to key hypothalamic and cortical feeding
THE EFFECTS OF HIGH-ENERGY DIETS ON MODULATORY LEARNING PROCESSES. ; Department of Psychological Sciences: Ingestive Behavior Research Center: Purdue University
Diets high in saturated fat and simple carbohydrates (HE
diets) have been associated with cognitive deficits in both human and nonhuman
animals. In rats, this type of “Western”
diet has been shown to disrupt learning processes that are dependent on the hippocampus,
such as spatial learning. The present
study further examines the effects of energy-rich diets on
hippocampal-dependent learning processes; particularly those that involve
modulatory learning that may be important to controlling food intake. A model developed in our laboratory suggests
that the inhibition of feeding behavior by neurohormonal “satiety” signals
occurs under conditions much like those that define a learning paradigm known
as a serial feature-negative discrimination.
To examine the influence of high-energy diets on this type of learning,
rats maintained on HE or standard chow diets were trained on this problem and
on other hippocampal-dependent learning tasks.
The results showed that rats fed the HE diet were impaired relative to chow
fed rats not only in solving the serial feature negative discrimination, but
also in other hippocampal-dependent, feeding-related, learning problems such as
food-sated extinction of conditioned appetitive behavior and discrimination
using 24-h and 0-h food deprivation levels as cues for food. These results
support the idea that high-energy diets may promote excess intake and weight
gain, in part, by altering hippocampal functioning in ways that may interfere
with some important learned controls of energy regulation.
COMPLEX HOMEOSTATIC ATTRIBUTES OF THE FOREBRAIN GLUCOSE-MONITORING NEURONAL NETWORK. ; Institute of Physiology and Neurophysiology Research Group of the Hungarian Academy of Sciences (HAS), Pécs University, Medical School
To study involvement of the forebrain glucose-monitoring (GM) neuronal network in the control of homeostasis, series of electrophysiological and behavioral experiments have been conducted in the rodent and macaque monkey. Single neuron recordings in anesthetized rats and alert primates elucidated characteristic activities of forebrain GM cells during: 1) microelectrophoretic administration of chemicals (such as the diabetes inducing streptozotocin /STZ/ or the primary cytokine interleukin 1beta /IL-1/; 2) gustatory stimulation, as well as 3) performing behavioral tasks. A single microinjection of STZ into various forebrain sites of Wistar rats caused type 2 diabetes like metabolic disturbances, and that of IL-1 was followed by hypophagia, hyperthermia, and metabolic alterations as well. These findings - along with results of our most recent fMRI studies in the rhesus monkey - indicate that intact functioning of the forebrain GM neuronal network is indispensable to protect the maintenance of homeostasis against the impact of environmental challenges.
Supported by: National Research Fund of Hungary (K 68431, M036687), Health Care Science Council (ETT 315/2006), NKTH MEDIPOLIS RET-008/2005, and the H.A.S.
*Present address: Department of Brain Science and Engineering, Kyushu Institute of Technology, Kitakyushu, Japan
A COGNITIVE-EXPERIMENTAL APPROACH TO REDUCING FOOD CRAVINGS AND MODIFYING EATING BEHAVIOUR. ; School of Psychology, Flinders University
Food cravings have been identified as an important precursor
to binge eating, itself a risk factor for obesity and eating disorders. Based
on converging evidence that visual and olfactory images are key components of
food cravings, this paper used a cognitive-experimental approach to suppress
such cravings and modify subsequent eating behaviour. In each of four
experiments, 90 undergraduate women (18-30 years) underwent a craving induction
procedure involving a combination of chocolate deprivation and exposure to
chocolate cues. They then performed either a visual, auditory or olfactory
imagery task. Participants rated their chocolate craving intensity after the
craving induction, and again after the imagery task. Following the imagery
task, participants also completed one of four behavioural measures of food
craving: a so-called chocolate tasting task (Exp.1), latency to begin a
taste-rating task (Exp. 2), speed of chocolate consumption (Exp. 3), and a
salivation measure (Exp. 4). As predicted, the visual and olfactory imagery
tasks were consistently superior to the auditory imagery task in reducing
participants’ craving for chocolate. However, these self-reported reductions in
craving did not correspond to any objective behavioural indicator. A
behavioural index of craving that is completely devoid of food or eating
connotations could perhaps prove more successful. Nevertheless, imagery-based
techniques in the visual and olfactory domain offer potential scope for
reducing food cravings in the context of problem eating behaviour.
RATINGS OF FULLNESS AFTER AD LIBITUM MEALS ARE NOT PREDICTED FROM RATINGS OF FULLNESS DURING INTERRUPTED MEALS IN PRESCHOOL CHILDREN. ; St. Luke's/Roosevelt Hospital
This study was conducted to determine whether ratings of fullness during meals, interrupted at fixed increments, predict fullness during an ad libitum meal in pre-school children. Demonstration of such a relationship would enable ratings of fullness to predict ad libitum intake, thereby greatly facilitating measurements of the satiating effects of foods. Eleven kindergarten students (four girls, seven boys; ages 5-6 years), were tested in five, 1-hour sessions, during their usual lunch time. After training them to rate fullness with pictures of varying sized portions of foods with a child-friendly scaling device (Appetite 47:233-243), children rated how full they felt after consuming each of 15, 15-ml portions of strawberry yogurt shake to a maximum of 450 calories, for four sessions. During the fifth session, they consumed 15 1-ml portions of the strawberry yogurt shake and then ate ad libitum from 800g of yogurt shake served in a closed container. After the second session, eight of the eleven children reliably increased ratings of fullness per unit eaten (p’s <0.05 on both days). However, the fullness ratings predicted for the ad libitum meal size, from the equations for ratings on the last two interrupted meals, were only marginally correlated (pearson r = 0.45, p = 0.26, spearman r = 0.61, p = 0.11). Physiological or environmental contextual controls of ratings may be different than during interrupted, than during ad libitum, uninterrupted, meals, and one cannot rely completely on one, to predict the other.
OROSENSORY STIMULATION DURING MODIFIED SHAM FEEDING INCREASES INTAKE OF SWEET SOLUTIONS MORE IN WOMEN WITH BULIMIA THAN WOMEN WITH ANOREXIA NERVOSA. ; 1Columbia University/NYSPI, 2Cornell/Weill Medical College
Although it is possible that abnormal meal size in humans is due to altered responsiveness of orosensory excitatory controls of eating, there is no direct evidence for this because food ingested in a test meal stimulates orosensory excitatory and postingestive inhibitory controls. We adapted the modified sham feeding technique (MSF) to measure orosensory excitatory control of intake of a series of sweetened solutions in the absence of postingestive negative feedback of ingested solution. Previously presented data showed that women with bulimia nervosa (BN) sipped more solution than women without an eating disorder in this procedure. In the present study, 14 women with anorexia nervosa (AN) were randomly presented with cherry Kool Aid® solutions sweetened with one of 5 concentrations of aspartame in a closed opaque container fitted with a straw. They were instructed to sip as much as they wanted of the liquid during 1-min trials and to spit the fluid into another opaque container, for 15 solutions per subject. Across all subjects, sweetener presence increased intake. Women with BN sipped more, and those with AN sipped less solution than controls. Over 3 trials, intake increased in women with BN, decreased in AN, and was stable in controls. Results further validate this MSF procedure, its ability to distinguish among eating disorder diagnoses, and hypotheses that women with BN have increased orosensory excitation, while non-binge eating women with AN, do not.
POTENT COMBINATION OF AMYLIN AND LEPTIN REDUCES FOOD INTAKE, BLOOD PRESSURE, AND OREXIGENIC NEUROPEPTIDES IN OBESE FBNF1 RATS . ; Florida State University
Leptin (LEP) reduces food intake and adiposity in rodents, but obesity induces leptin resistance. Amylin (AMN) transiently reduces food intake in lean and obese rats. We tested the synergistic effects of AMN and LEP in combination (AMN+LEP) in lean and obese rats. Male rats were implanted with arterial catheters and fed a 32% (OBESE) or 4% (LEAN) fat diet for 5 months. Rats were given 7-day subcutaneous infusions of saline (SAL), AMN (100μg/kg/d), LEP (300μg/kg/d), or AMN+LEP via osmotic pump. LEP reduced food intake by 21% in LEAN rats but was ineffective in OBESE rats. Amylin reduced food intake by 27% in LEAN and OBESE rats. AMN+LEP synergistically reduced food intake by 58% in LEAN (SAL:63±2 LEP:50±2 AMN:48±2 AMN+LEP:27±3 kcal/d) and OBESE rats (SAL:68±4 LEP:65±5 AMN:48±9 AMN+LEP:28±5 kcal/d). The similar decrease in AMN+LEP rats suggests that leptin sensitivity may be restored in OBESE rats. LEP and AMN+LEP also reduced blood pressure by 7-8mmHg. Further, AMN+LEP synergistically reduced fat mass in LEAN (SAL:12.1±0.4 LEP:9.6±0.4 AMN:9.0±1.1 AMN+LEP:4.2±0.5 g) and OBESE rats (SAL:24.8±1.1 LEP:21.3±1.8 AMN:19.2±2.4 AMN+LEP:14.7±1.6 g). In obese rats, AMN+LEP decreased melanin-concentrating hormone and orexin gene expression and prevented a rise in suppressor of cytokine signaling-3, an inhibitor of leptin. These results demonstrate that this combination may be an effective treatment for obesity where either alone is insufficient.
RICE AND SUSHI CRAVINGS: A PRELIMINARY STUDY OF FOOD CRAVING AMONG JAPANESE STUDENTS. ; Tohoku University
The objectives of this study were to develop a Food Craving Inventory for Japanese (FCI-J) and to investigate the phenomenon of food craving among Japanese students. One hundred and eighty-five female college students completed the newly developed FCI-J. Factor analysis yielded conceptual factors that were interpreted as sweets, snacks, Western foods, sushi, and rice. Test-retest and internal consistency analyses indicated good reliability for both total score and score of subscales. In addition, results showed that the FCI-J has good content, concurrent, construct, and discriminant validity. It is worth noting that “rice craving” may be characteristic among Asian rice-consuming countries, and that there are considerable “sushi cravers” in Japan. These findings suggested that the craving for some kinds of food is influenced by the tradition of food products and cultures. I will also be presenting data on Japanese males.
SEROTONIN 2C RECEPTOR (5HT2CR) SIGNALING IS INVOLVED IN LPS-INDUCED NEURONAL ACTIVATION AND ANOREXIA. ; Institute of Animal Sciences, ETH Zurich
LPS, a potent activator of the innate immune system, is commonly used to investigate the acute phase response to infection, including anorexia. 5HT2CR signaling has been shown to be involved in the mediation of LPS anorexia. Here we used the selective, potent and brain-penetrant 5HT2CR antagonist SB 242084 in an attempt to identify the brain sites involved in LPS-induced anorexia. Male Long Evans rats received 1 ml/kg intraperitoneal (ip) injections of 0 or 0.3mg/kg SB 242084 and 1 h later at dark onset an additional ip injection of 0 or 100 μg/kg LPS. Food intake was measured in one set of rats and c-Fos immunoreactivity (a marker of neuronal activation) in another, unfed set 90 min after LPS injection. As previously reported (von Meyenburg et al., Pharmacol. Biochem. Behav. 74:505-512, 2003) SB 242084 markedly attenuated the LPS-induced reduction in food intake, with no anorexia evident for the first 4 h after LPS. SB 242084 also blocked the LPS-induced increases in c-Fos expression in the paraventricular nucleus, central nucleus of the amygdala, nucleus tractus solitarius, A1 noradrenergic cells, raphe pallidus nucleus, median raphe nucleus and dorsal raphe nucleus. SB 242084 did not alter c-Fos response in the arcuate nucleus (Arc) or the raphe magnus nucleus (RMg). These data indicate that 5HT2CR signaling activates a diffuse neural network, presumably mediating anorexia and other responses to LPS; they suggest that the Arc and the RMg neurons that express c-Fos after LPS are not necessary for LPS anorexia.
POST-INGESTIONAL SIGNALS AND DEPLETION-INDUCED WATER AND SODIUM INTAKE. . ; University of Cincinnati
This study examined the role of post-ingestional signals in the water and salt intake that follows dehydration or sodium depletion. Rats were implanted with gastric fistulas and 10 days later were deprived of water over night. Water was returned and intakes were recorded at 15,30,60, and 120min with gastric fistulas open (sham drinking) or closed (control). At all times sham drinking rats had greater intakes when compared to controls. Water intakes of control rats ceased to increase after 30min whereas the intakes of sham drinking rats increased over time. To evaluate the contribution of post-ingestional signals to water and salt intake after sodium depletion rats were given sodium deficient chow for 48h. Next, rats were given furosemide (10mg/kg) and urine was collected. 24h later, rats were given 0.5M NaCl and intakes were measured at 15,30,60, and 120min. After 120min, rats were sacrificed and plasma sodium (pNa) was measured. Though both groups lost ≈ 2.2mEq of sodium after furosemide, sham drinking rats consumed more water at all times and more 0.5M NaCl at 30,60, and 120min compared to their real drinking counterparts. Control rats ceased to increase 0.5M NaCl intake after 30min, whereas the intakes of sham drinking rats increased over time. At 120min sham drinking rats consumed 7.5mEq of sodium nearly twice that of controls, but had lower pNa. Interestingly, the ratio of water to 0.5M NaCl intake was similar in both groups, with each making a mixture of ≈ 0.25M NaCl. The results suggest that post-ingestional signals are necessary for the satiation of water and salt intake elicited by dehydration or sodium depletion.
VENOUS VERSUS CAPILLARY BLOOD FOR THE PURPOSES OF POSTPRANDIAL GLUCOSE TESTING IN HUMANS.. ; University of Rhode Island
Capillary blood has been suggested as preferable to venous blood when measuring glucose in the postprandial state, because capillary blood is in direct exchange with tissues. However data are lacking within subjects. Thus, we measured both venous and capillary blood in 50 healthy young adults (37F&13M; age 19+2 y; BMI=23+3) who had fasted overnight. Subjects then consumed a mixed macronutrient test shake with energy content equal to 25% of their estimated resting energy expenditure. Thirty minutes after consumption, venous and capillary sample were again obtained. Capillary blood was measured immediately by an automated analyzer (Hemocue, Angleholm, Sweden) and venous blood was centrifuged to plasma and analyzed by Cobas Mira Plus (Roche Diagnostics, NJ, USA). Venous blood was also analyzed by RIA for ghrelin (Linco Diagnositics, St, Charles, MO, USA) and ELISA for insulin (Mercodia, Uppsala, Sweden). In the fasting state, glucose values did not differ between venous and capillary samples (88+9 vs 89+12 mg/dl; p=.884), and were correlated (r=.472; p=.001). Postprandially, venous and capillary glucose were still correlated (r=.719; p=.000), but venous samples showed a significantly lower glucose concentration than capillary samples (102+25 vs 119+27 mg/dl; p=.000). Neither venous nor capillary glucose correlated with ghrelin, but postprandial (not fasting) insulin correlated with venous (r=.496; p=.001) and capillary (r=0.428; p=0.005) glucose. These findings further support previous suggestions that capillary blood glucose may be a preferable measure in studies considering factors such as glycemic index.
EFFECT OF HISTONE DEACETYLASE INHIBITION BY NAB ON LICL-INDUCED C-FOS EXPRESSION IN THE AMYGDALA.. ; Dept Biological Science, Prog Neuroscience, Florida State Univ.
Gene expression is controlled not only by transcription factors binding promoter DNA, but also by dynamic changes in chromatin structure. Chromatin acetylation in the transcriptional region is necessary for optimal gene expression, and expression may be increased by inhibiting histone deacetylase (HDAC) activity. In the hippocampus, for example, it has been shown that inhibition of HDAC by trichostatin A or sodium butylate (NaB, 1.2 g/kg) induces a high level of histone acetylation and intensifies c-fos and c-jun mRNA expression after kainate stimulation. Continuing our studies on gene expression in the central amygdala (CeA) in conditioned taste aversion (CTA) learning, we investigated if c-Fos expression in the CeA is correlated with histone acetylation and regulated by HDAC. We examined phospho-acetyl-histone H3 (pAH3) and c-Fos expression by immunohistochemistry following systemic NaB. Rats were sacrificed 0.5, 1, 3, 6 and 9 h after NaB or 1 h after saline injections. A high dose of NaB (1.2 g/kg, 0.9 M, ip) highly increased pAH3 at 0.5 h and 1 h and c-Fos at 1 h. This effect could be explained by the hypertonicity of the treatment, however, because an iso-osmotic control (0.9 M NaCl) also increased pAH3 and c-Fos in the CeA. A low dose of NaB (0.4 g/kg, 0.3 M) increased pAH3 but not c-Fos at 0.5 h in the CeA. Thus, a low dose of NaB should be employed to avoid the effects of stress. We also examined changes in specific acetylation of histone H3 and H4 by western blot. Future studies will examine the effect of NaB on CTA and LiCl-induced c-Fos.
INTERACTION BETWEEN THE HEPATIC VAGUS AND THE MELANOCORTIN SYSTEM IN DIET-INDUCED OBESITY . ; Dept Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience
Previously, we showed that the hepatic vagus alters the feeding response to a high fat diet in diabetic rats and affects proopiomelanocortin (POMC)mRNA. This suggests that, at least in diabetic rats, the hepatic vagus contributes to the response of the melanocortin (MC) system to fat eating. The question remains whether the hepatic vagus is also involved in the response to a palatable diet in non-diabetic rats. We determined whether the hepatic vagus is involved in the response to a choice diet with saturated fat and sugar in addition to chow (HFHS-choice diet) via an interaction with the MC-system. We hypothesized that the hepatic vagus via interaction with the MC-system would inhibit fat intake and hepatic vagotomy (HV) would therefore increase lard intake when on a HFHS-choice diet. In contrast to our hypothesize, HV decreased lard intake and increased sucrose intake, however did not affect total intake. Interestingly, the changes in preference observed in HV rats did not occur when lard or sugar was presented seperately in addition to chow. Thus, unlike what has been shown for diabetic rats, HV affects the preference for sucrose over lard in diet-induced obese rats on a HFHS-choice diet. We next determined MC expression and receptor binding. On a HFHS-choice diet, HV rats showed increased MC activity compared to sham rats, which could reflect a compensatory mechanism to prevent hyperphagia. We, therefore, conclude that when hepatic vagotomized , the MC-system reponds to balance the lack of food intake inhibition by the vagus.
BOMBESIN RECEPTOR SUBTYPE-3 MRNA IS INCREASED IN THE HYPOTHALAMUS OF DIET-INDUCED OBESE RATS. . ; John Hopkins University School of Medicine
Bombesin receptor subtype-3 (BRS-3) is a G-protein coupled receptor that shares ~50% homology with other mammalian bombesin receptors. There is currently no known endogenous ligand for BRS-3 and it is classified as an orphan receptor. Mice with a targeted deletion of BRS-3 develop obesity, hypertension, impairment of glucose tolerance and insulin resistance suggesting that BRS-3 participates in energy homeostasis. We have shown that arcuate (Arc) BRS-3 mRNA was increased by 48 h fasting and decreased by central leptin injection suggesting that BRS-3 expression is responsive to energy regulatory signals. To further identify factors that regulate BRS-3 in normal animals, we evaluated the effects of prolonged access to a high fat (HF) diet on hypothalamic BRS-3 gene expression. Male Sprague-Dawley rats were provided with HF (60%) or low fat (LF, 10%) pelleted food for 14 weeks. During the final 4 weeks, rats on the HF diet were also given ad lib access to Ensure liquid diet. Rats were then sacrificed and brains collected for measurement of BRS-3 mRNA using RT-PCR. Rats on the HF diet had significantly greater adiposity than those on the LF diet. BRS-3 expression in the Arc was increased two-fold in HF fed rats compared to rats fed the LF diet. Previous studies reported that HF diet-induced obesity results in the failure of leptin to modulate peptide secretion and initiate the leptin signaling cascade. Because the results from the present study were opposite to those after central leptin administration, this suggests that BRS-3 gene regulation may depend upon intact leptin signaling.
PERIPHERAL ENERGY SENSING IN THE CONTROL OF EATING &NDASH; NEW DEVELOPMENTS. ; Institute of Animal Sciences, ETH Zurich
Since Russek first proposed the existence of a hepatic glucosensitive mechanism of satiety (Nature 197:79, 1963), the role of the liver, in particular the vagally innervated hepatic portal area, in eating has been the focus of intense research. The basic concept of this hepatic control of eating has been that metabolites and hormones that are released into the hepatic portal vein in relation to meals, or meal-related metabolic events, somehow modulate vagal afferent signaling, which eventually affects eating. While this mechanism has been shown to be true for glucagon (Geary et al, Am J Physiol 264:R116, 1993) and appears to be also valid, at least to some extent, for glucose (Tordoff & Friedman, Am J Physiol 251:R192, 1986) and cholecystokinin (Eisen et al, Am J Physiol 289:R456, 2005), only inconsistent, weak evidence supports a hepatic mechanism of action for other peripheral events implicated in eating control, such as fatty acid oxidation. In this presentation I will review the current status of the hepatic control of eating and present an alternative working hypothesis, that fatty acid oxidation in enterocytes may affect eating by modulating the activity of vagal afferents originating from the intestine. Finally, I will review some evidence suggesting intestinal vagal afferents may also be involved in the eating-inhibitory action of glucagon-like peptide-1 (GLP-1).
ANATOMICAL DIFFERENTIATION OF THE SUPPRESSIVE EFFECTS OF INSULIN ON TWO FOOD REWARD TASKS. ; 1VA Puget Sound Health Care System, 2University of Washington, 3Seattle Institute for Biomedical and Clinical Research, 4University of Latvia
We have previously reported that intraventricular (IVT) insulin administration decreases food reward in the rat. Because multiple sites comprise the CNS reward circuitry and are insulin-responsive, we evaluated the contribution of several reward sites to the suppressive effects of IVT insulin on two food reward tasks. The mu opioid agonist DAMGO (3 nmol) increased (p<0.05) 60-min sucrose pellet intake (176+29, 191 +33, 164+21, and 225+30% of paired artificial cerebrospinal fluid (CSF) control intakes, for the bilateral arcuate (ARC) and paraventricular (PVN) nuclei of the hypothalamus, and, unilaterally, the nucleus accumbens shell (uniNAcc) or ventral tegmental area (uniVTA), respectively). Insulin (5 mU) had no effect on baseline sucrose intake but decreased (p<0.05 vs. DAMGO) DAMGO-stimulated sucrose intake when co-administered into the uniVTA (DAMGO/insulin intakes: 182+34, 172+24, 155+19, and 141+22% of paired CSF intakes for ARC, PVN, uniNAcc, and uniVTA, respectively). Additionally we tested the effect of acute administration of 5 mU insulin on 5% sucrose self-administration. Insulin decreased (p<0.05) lever presses for sucrose rewards only within the ARC (75+5, 99+12, 106+10, 100+15, 127+16, and 89+7% of paired CSF controls, for ARC, PVN, unilateral NAcc or VTA, and bilateral NAcc or VTA, respectively). These findings suggest that insulin-induced suppression of different aspects of food reward is mediated by multiple CNS sites.
REGULATION OF FOOD REWARD BY ADIPOSITY SIGNALS. ; 1VA Puget Sound Health Care System, 2University of Washington
Several lines of evidence suggest that peripheral adiposity signals such as insulin and leptin can downregulate functional aspects of CNS reward circuitry. Performance in a variety of behavioral paradigms that assess different components of reward can be enhanced by food restriction, and blunted by insulin and leptin. These include electrical self-stimulation; acute licking of sucrose solutions; opioid-stimulated sucrose intake; sucrose self-administration; and food-conditioned place preference. Evidence suggests that not only energy status, but also diet composition, may modulate motivated work for palatable foods. Our findings suggest that adiposity signals interact with both dopaminergic and opioidergic mechanisms that underlie intake of palatable foods independent of caloric need. We have been identifying critical CNS targets for the actions of insulin and leptin in these paradigms. Findings to date will be reviewed. Ventral tegmental area dopamine (DA) neurons are one target, as they express insulin and leptin receptors, and demonstrate activation of cell-sginaling pathways in response to direct administration of either insulin or leptin. Terminal projects in the striatum are also a target: Insulin regulates the synthesis,and DA terminal concentrations, of the DA transporter which clears DA from the synapse. The latter action is rapid and dependent upon PI3kinase activation consistent with insulin signaling mechanisms in the hypothalamus. Implications of this work for human food choice and obesity, and new directions for study, will be discussed.
THE INVOLVEMENT OF INTERLEUKIN-1 IN THE ACTIONS OF GALANIN-LIKE PEPTIDE ON ENERGY BALANCE. ; University of Manchester
Galanin-like peptide (GALP) is a neuropeptide that is thought affect energy balance by actions within the central nervous system. GALP plays a dichotomous role in energy homeostasis in rats; producing orexigenic effects in the short-term, but anorexigenic effects over the longer-term. In mice, GALP produces only anorexigenic actions. Recent data suggest that GALP promotes feeding via activation of known orexigenic neurones (neuropeptide Y and orexin), but the mediators of the anorexic effect are unknown. The anorexic actions of GALP are similar in magnitude and profile to those seen after central injection of the cytokine interleukin-1 (IL-1). Thus, we tested the hypothesis that IL-1 mediates the effects of GALP on energy balance. Intracerebroventricular (icv) injection of GALP in male Sprague-Dawley rats stimulated food intake over 1h, but decreased feeding and body weight at 24h, and caused a rise in core body temperature over 8h. These longer-term actions were inhibited by co-infusion of the IL-1 receptor antagonist, IL-1RA. However, IL-1RA had no effect on the GALP-induced acute stimulation of feeding at 1h. Mice that were defective in the IL-1 system e.g. IL-1 knock out mice, were partly resistant to the effects of GALP on body weight and body temperature. GALP injection (icv) also stimulated production of IL-1 protein in microglia and macrophages in selected brain areas, such as the peri-ventricular brain region, meninges and choroid plexus. These data suggest GALP induces expression of IL-1 in the brain and the anorexic and febrile actions of GALP are mediated by this cytokine.
BINGE EATING AND NIGHT EATING IN OBESE BOYS AND GIRLS. ; St. Luke's Hosp, Columbia U.
Abnormal eating behaviors in childhood may lead to future weight gain and increase eating disorder risk in adults. The study aim was to examine associated psychopathology of binge eating and night eating in obese adolescents. 65 participants (33b:32g, 12-18yr) were recruited from pediatric psychiatry clinic and completed six questionnaires: Questionnaire on Eating and Weight Patterns-Revised(QEWP-R), Emotional Appetite Questionnaire(EMAQ), Perceived Stress Scale(PSS), Quick Inventory of Depressive Symptomatology(QIDS), Night Eating Diagnostic Questionnaire(NEDQ), and Eating Habit Checklist(EHC). Diagnostic categories (based on QEWP and NEDQ) were created for binge eating (BE, n=21;non-BE, n=40) and night eating (NE, n=11;nonNE, n=52). ANCOVAS with gender as a fixed factor and BMI percentile (98.7+/-1.5SD) as a covariate showed that BE had more depressed mood than the nonBE (8.7+/-6.3vs6.8+/-3.9)p=.01, as did the NE vs nonNE (10.1+/-7.1vs6.1+/-4.7)p =.02. For the EHC, the BE showed more disturbed eating than the nonBE (29.8+/-7.8vs22.11+/-4.8) p=.001, as did NE vs nonNE(29.4+/-6.7vs23.8+/-6.6) p=.009. No significant interaction by gender or BMI percentile was found for QIDS or EHC. In the EMAQ, negative emotional eating did not differ for BE and non-BE but was greater for NE than nonNE in girls(5.6+/-1.1vs3.8+/-1.1)p=.004. PSS was not greater in BE or NE. To conclude, BE was associated with depressed mood while NE was associated with negative emotional eating among the girls. The different associated psychopathologies of NE and BE is consistent with distinct diagnostic entities.
MATERNAL CONTROL OF FEEDING IS ESTABLISHED DURING THE FIRST SIX MONTHS OF INFANCY: DIFFERENCES BETWEEN BREAST-FEEDING AND FORMULA-FEEDING MOTHERS.. ; Dept Psychology, Swansea University
A high level of parental control of feeding in early childhood has been shown to have negative effects on child weight and eating patterns. Maternal over-control has been associated with disinhibited eating, poor awareness of internal signals, lack of self-regulation of intake, and increased risk of overweight. Most studies are based on children over 3 years, but more recently reports have suggested that high levels of maternal control are evident much earlier in childhood. For example, mothers who breast-fed their infants appeared to exert low levels of control over child feeding at 1 year; a pattern which seemed to be fixed as similar results were found from a follow-up study at 2 years (Blissett and Farrow 2007, IJO). The current study examined differences in self-reported levels of control in women (N=362) who had either breast-fed or formula-fed from birth. Mothers completed a modified version of the CFQ (Birch et al. 2001, Appetite) based on their experience of feeding an infant before from birth to 6 months, prior to the introduction of solid foods. Mothers who breast-fed demonstrated lower levels of control in terms of both restriction of milk feeds and pressure to consume (P<0.01 in both cases). However, breast-feeding mothers were more likely to use feeding for comfort (P<0.01). These data suggest that maternal feeding style develops from birth and may be determined before weaning occurs. These findings may partially explain why breast-feeding protects against overweight and obesity.
EFFECTS OF EATING DESSERT-SPECIFIC VS. DESSERT NON-SPECIFIC FOOD ON THE REWARDING VALUE OF FOOD IN GENERAL . ; 1Human Biology, Maastricht University, 2Top Institute Food and Nutrition
Background: Human eating behavior is changed non-homeostatically by the rewarding value of food: liking (palatability) and wanting (incentive motivation). Objective: How is the rewarding value of food affected by eating dessert-specific (chocolate mousse) vs. dessert non-specific food (cottage cheese)?
Methods: Our subjects (10m/20f, age 28.2±9.0yrs, BMI 24.2±3.3kg/m2, randomized cross-over design), were tested twice in a fasted condition. They played computer games to quantify liking and wanting for 72 items divided in 6 categories (bread, filling, drinks, dessert, sweets, stationary). Liking was quantified from the relative preference of paired items (within and between categories) and wanting by playing memory games to earn items to choose from. The games were played before and after consumption of chocolate mousse or cottage cheese, both matched for energy content (5.6kJ/g) and daily energy requirements (10%).
Results: Chocolate mousse was liked more than cottage cheese (p=0.0016). Wanting for any food was decreased more after eating chocolate mousse (p<0.0001) than after eating cottage cheese (p=0.1539). Chocolate mousse, but not cottage cheese, induced a switch in relative liking between categories, decreasing the dessert category (p=0.0004) and increasing the stationary category (p=0.0023).
Conclusion: Eating dessert-specific food decreases wanting of food generally more than eating less liked, dessert non-specific food.
CHRONIC ANTAGONISM OF MU OPIOID RECEPTORS IN THE NUCLEUS ACCUMBENS ATTENUATES DEVELOPMENT OF DIET-INDUCED OBESITY IN RATS. ; Pennington Biomedical Research Center, Louisiana State University System
The nucleus accumbens is recognized as key brain structure involved in reward seeking by translating motivation into action; more specifically, it is suspected to help drive consumption of palatable food. It has been shown that activation of accumbens mu opioid receptors disinhibits a voracious appetite, especially for palatable or high fat food. We have demonstrated an effector pathway in this response involving hypothalamic orexin neurons and orexin signaling in the ventral tegmental area. Here we show that chronic antagonism of mu opioid receptor signaling in the nucleus accumbens of Sprague-Dawley rats by means of repeated local injection of β-funaltrexamine (BFNA) significantly attenuates hyperphagia and palatable diet-induced obesity. BFNA injected bilaterally (10 nmol/side) every 4-5 days attenuated palatable diet-induced weight gain (73 ± 7 vs. 107 ± 10 g; p <0.01) and excess fat deposition by 50% (p <0.05). BFNA reduced cumulative high-fat chow intake (991 ± 70 vs. 1290 ± 62 kcal; p <0.01) and total food intake (3042±61 vs. 3343±78 kcal; p <0.05), but had no effect on Ensure intake. In contrast, when fed regular chow, BFNA had no effect on weight gain, adiposity, and food intake. We conclude that endogenous mu opioid receptor signaling in the nucleus accumbens contributes to the development of palatable diet-induced obesity by a mechanism at least partially dependent on hyperphagia. Supported by DK071082.
GENDER DIFFERENCES IN BASIC TASTE PERCEPTION. ; Department of Psychology, University of Haifa
Gender differences are documented in smell, pain and colour perception. Gender differences in taste responses in rats are known. However, despite occasional observations of gender differences in human taste perception, there are no systematic studies. Here we assessed gender differences in intensity and hedonics of 6 concentrations each of NaCl, citric acid, sucrose and quinine HCl using linear visual analogue scales. Men (n=53) reported lower intensity of taste than women (n=41). Specifically men reported NaCl, citric acid and quinine HCl as less intense, but not sucrose. Despite these perceptual differences, hedonic evaluation only differed for quinine, men finding it less aversive then women. Menstrual cycle marginally influenced perception of taste intensity and hedonics, and did not account for the gender differences. Smoking, age (23-35y), hunger, and cuisine (Ashkenazi vs Sephardi) influenced assessment of specific tastes, but BMI did not. However, these variables did not detract from the gender differences. Men and women experience basic tastes differently. Whether these differences are significant to daily ingestive behavior requires further inquiry.
FOOD POWER SCALE PREDICTS DESSERT EATING, BUT NOT MEAL EATING OR PORTION SIZE EFFECT. ; Cornell University
Two paper and pencil tests of eating behavior, Herman and Polivy’s Restraint Scale and Lowe’s Food Power scale were examined for their capacity to predict the portion size effect, the amount consumed at a meal, and dessert eating (as a measure of eating in the absence of hunger). Eighty-eight students were asked to eat lunch in the Cornell Metabolic Unit on two occasions, one week apart. Prior to the first meal, the subjects completed the Restraint Scale and the Food Power Scale. The lunch then offered buffet styled. The amount of food the participants removed from the buffet table and the amount they consumed were determined by weighing. Food for the second lunch consisted at the same foods the subjects ate the previous week but served restaurant style and in amounts equivalent to 150 percent of the foods served at first meal. Measures of hunger and satiety were taken before and after consuming each meal. After the second meal, the subjects were offered chocolate cake and ice cream for dessert. A significant portion size effect was observed indicated by a greater consumption of the second meal (minus the dessert) relative to the first. The consumption of the second meal caused a significantly greater reduction in hunger and increase in satiety than the first meal. Despite the increased feeling of satiety almost all subjects consumed dessert. The Restraint Scale failed to predict any the portion size effect or any other aspect of eating behavior. The Food Power scale also failed to predict the portion size effect by was a significant predictor of the amount of dessert consumed.
THE INFLUENCE OF WARMING AND COOLING OF THE TONGUE ON THE ACTIVITY OF ETHANOL/SUCROSE-RESPONSIVE NEURONS IN THE PARABRACHIAL NUCLEI IN THE HAMSTER . ; Southern Illinois University
It is known that some gustatory neurons in the nucleus of the solitary tract (NST) and gustatory fibers in the chorda tympani (CT) respond to thermal stimulation of the anterior tongue. It is also known that some taste cells in the NST and gustatory fibers in the CT respond to ethanol (EtOH) stimulation, and that EtOH effectively activates sucrose-best cells or fibers in rodents. In humans, anterior tongue stimulation produces sweet sensation, suggesting that there is a close association between warming and sweet taste. The parabrachial nuclei (PbN) in the pons are the second taste relay of the central taste pathway in the rodent. Gustatory responses of taste neurons in the NST and PbN are modulated by various physiological factors related to ingestive behavior. The purpose of the present study was to investigate the effect of warming and cooling of the tongue on neuronal activity of EtOH/sucrose-sensitive neurons in the hamster PbN. In the first set of experiments, 55 gustatory PbN neurons were recorded extracellularly in response to four basic taste stimuli, 25% EtOH, and 40°C and 4°C distilled water in the urethane-anesthetized hamster. Among these 55 taste-responsive PbN neurons, 32, 28, and 36 neurons responded to 25% EtOH, 40°C and 4°C distilled water, respectively. The response to 25% EtOH was positively related to sucrose response (r = 0.82, p <0.001). In the second set of experiments, 30 sucrose-sensitive neurons in the PbN were recorded, in response to a series of EtOH concentrations (3 – 40%) alone and mixtures with 32 mM sucrose at room temperature, 40°C and 4°C. Neuronal responses to EtOH at room temperature (26°C) and 40°C increased as the concentration was raised. The response to a mixture of EtOH and sucrose was greater than EtOH or sucrose responses alone. The responses of EtOH alone or EtOH/sucrose were enhanced by applying solution at 40°C but were flat at 4°C. These data demonstrate that EtOH responsiveness is closely associated with sucrose sensitivity in the PbN taste neurons, and that warming augments this interaction. Supported by NIDCD 006623.
SYNPHILIN-1 INDUCES HYPERPHAGIA-MEDIATED OBESITY IN MICE. ; Department of Psychiatry and Behavioral Science, Johns Hopkins University School of
Synphilin-1, a synaptic vesicle protein with unclear function, was originally identified as a protein that can interact with alpha-synuclein and parkin. Synphilin-1 is shown to promote the formation of intracellular inclusions and may play a protective role in Parkinson’s disease. We found that expression of synphilin-1 in neurons in mice by a PrP promoter resulted in increased body weight, body fat and elevated plasma levels of insulin and leptin, and insulin insensitivity. We further found that the obesity in synphlin-1 mice likely results from increased energy intake as synphilin-1 mice had increased daily food intake but no changes in daily activity compared with none transgenic mice. Pair feeding synphilin-1 mice to amounts consumed by intact non transgenic mice normalizes body weight, body fat and elevated insulin and leptin levels. We have identified high levels of synphilin-1 expression in the anterior hypothalamus, arcuate and paraventricular nuclei suggesting that the altered food intake derives from alterations in hypothalamic function. These data identify a novel potential role for synphilin-1 in energy balance.
SHAM FEEDING INCREASES OPERANT MEASURES OF SUCROSE REWARD IN RATS. . ; Penn State Univ.
Sucrose is inherently rewarding to both humans and rodents. When rats ingest a sucrose solution, however, fluid in the GI tract rapidly induces neural and hormonal signals that terminate intake. We hypothesized that the absence of satiety signals not only maintains, but actually increases the reward value of sucrose. After gastric fistula implantation,16 S-D rats were tested on fixed ratio (FR) and progressive ratio (PR) schedules as an index of the reward strength of 5 different concentrations of sucrose, 0.03M, 0.1M, 0.3M, 1.0M, and 2.0M. After 3 days of habituation, 8 rats were tested while sham feeding on an FR10 and the first PR5 schedule, and then when real feeding on a second PR5. Another 8 rats had the order reversed, real feeding during the FR10 and the first PR5, then sham feeding on the second PR5. The data revealed that, regardless of test order, sham intake increased the reward value of the 1.0M and 2.0M sucrose solutions. On an FR10, sham feeding rats ingested significantly more sucrose than when real feeding at 1.0M (32.3±5.2 vs. 13.8±1.1) and 2.0M (31.9±5.4 vs. 10.8±1.2). The PR5 data exhibited differences in break point, a measure of reward strength, depending on prior experience. During sham intake, the break points for sham-real rats were 53 and 100 licks higher for 1.0 and 2.0 M sucrose, respectively, than when they real fed. The same differences were 20 and 56 licks, respectively, for real-sham rats. Overall, this study shows that reducing GI feedback increases the apparent reward value of strong sucrose solutions. Support: NIH DC00240, DA009815, PA State Tobacco Settlement Award.
THE APPETITE CONTROL BENEFIT OF A FUNCTIONAL LOW FAT YOGURT. ; Danone Research
Getting energy intake adapted to energy requirements, while maintaining control of appetite and regular eating patterns is a key strategy for weight management. In line with the eating frequency concept, the consumption of healthy snacks driven by hunger may be of interest, if not leading to overeating. In this context, the food industry has to offer to consumers low-energy dense products of high nutritional quality, which reduce appetite feelings between meals. Thus, various protein and fibre enrichments of a low fat dairy matrix were first checked for their satiating potential in healthy women (SSIB 2007). Then, a protein and fibre enriched low fat yogurt was designed and compared in clinical trials to a non-enriched low fat yogurt. A first randomised, crossover, study showed the efficacy of a serving (120g, 75kcal) of the enriched yogurt, consumed as a mid-morning snack, in significantly reducing appetite feelings (hunger, fullness, desire to eat, prospective consumption and satisfaction) over the 2 next hours. The same methodology was applied in a larger multi-centre study, with the additional assessment of energy intake at lunch. The subjective appetite-reducing effects observed in the first study were confirmed and even strengthened by the significant decrease in energy intake (65 kcal) at lunch. The appetite control benefit of the protein and fibre enriched yogurt was also perceived by consumers after 2 weeks of daily consumption in free living conditions. Future studies should aim at assessing longer-term effects of protein and fibre enriched low-fat yogurt as a helpful tool for daily appetite control and weight management.
CHARACTERIZATION OF MICE LACKING THE GENE FOR CHOLECYSTOKININ . ; 1Department of Pathology and Laboratory Medicine, University of Cincinnati, 2Department of Psychiatry,University of Cincinnati, 3Department of Molecular and Integrative Physiology, University of Michigan, 4Department of Anatomy, Physiology and Cell Biology, University of California
Cholecystokinin (CCK) is released in response to feeding and it functions in the modulation of feeding, exploratory and memory activities. The present study determined fat absorption, body composition and food intake of CCK knockout (CCK-KO) mice by utilizing the non-invasive measurement of fat absorption with quantitative magnetic resonance imaging and DietMax system, respectively. Additionally, exploratory and memory capacities were assessed by monitoring running wheel activity, elevated plus-maze and Morris water-maze tests. Compared to wild-type controls (WT), CCK-KO mice had normal food intake, fat absorption, body weight and body fat mass. CCK-KO mice ate more food than WT controls during the light period. Energy expenditure was unchanged between the genotypes; however, CCK-KO mice displayed greater fatty acid oxidation. CCK-KO mice were as active as WT animals in the running wheel test. CCK-KO mice spent more time in the closed arms of an elevated plus-maze, indicative of increased anxiety. Additionally, CCK-KO mice exhibited attenuated performance in a passive avoidance task and in the Morris water maze. We conclude that CCK is involved in the regulation of food intake and metabolic rate and is important for memory and exploration.
EFFECTS OF THE VARIETY OF WATER AND FOOD ON FEEDING BEHAVIOR IN RATS . ; Research Center in Feeding Behavior and Nutrition CUSur University of Guadalajara
Evidence of regulation front a variety of flavors is contradictory. Rolls (1990) affirmed that, in presence of a variety of foods, organisms consume greater amount of food due to a phenomenon that denominated sensory specific satiety. The objective of this experiment was to evaluate effects of variety of water and food on feeding behavior in rats. Twenty ford albino rats were used, 12 females and 12 males. They were exposed to a deprivation program of 22 hours. Purina Lab Chow and water were used like basal diet. Three types of diet (hipercaloric, normocaloric and hipocaloric) and two flavors to add to the water were used like experimental diet. The subjects were assigned randomly to four groups. The experiment was divided in 4 phases. All groups received basal diet in phases 1 and 3. There were two conditions en phases 2 and 4. All groups received basal diet in firs condition (1 hrs). Firs group received food variety in second condition. Second group received water variety and third group received water and food variety. Finally, control group received basal diet in both conditions.The results show that the subjects exposed to the variety of food and water were the group that presented the greater consumption.
WHY SOME PEOPLE EAT IN EXCESS OF THEIR ENERGY REQUIREMENTS: A NEW THEORY OF FOOD REGULATION.. ; 1University of Auckland, 2University of Firenze
Pleasure guides the initiation and cessation of eating. Non-homeostatic eating occurs only when the perceived pleasure of eating exceeds that of eating in a homeostatic manner. Eating pleasure is determined by:
1. Sensations aroused by the food
2. The epigastric empty hollow sensation (EHS)
3. Low mental arousal (settled alertness)
Traditionally people seek more and tastier foods to attain pleasure - a ground for food addiction. The onset of EHS motivates homeostatic eating followed by markedly increased eating pleasure. Recession of the EHS during satiation signals pleasurable eating cessation. The whole process potentiated by settled alertness.
While the EHS is innate, its significance must be learned. A form of inattentional blindness to this interoceptive sensation appears common. Recognition of the EHS with the cultivation of settled awareness should result in better regulation of energy intake.
Cannon’s work on hunger upholds the EHS as a significant sensation distinct from emotion.
That the maximisation of pleasure leads to efficacious behaviour has been suggested by Cabanac.
Work suggests that hunger and thirst must be learned in humans and in animals.
Innovative work by Ciampolini et. al. gives evidence that subjective cues are significant in homeostatic eating.
In anorexia nervosa and obesity subjects are unable to recognise internal eating cues.
Clinical improvement has been noted in diabetes, gastritis, rheumatoid arthritis, inflammatory bowel disease and Graves’ disease among patients taught to recognise the EHS.
RESTRAINED EATING, HEDONIC HUNGER AND FOOD REWARD: AN FMRI STUDY . ; Drexel University
Restrained eaters (RE) engage in counterregulatory eating, but research has shown that this is not due to low-calorie dieting. It may stem from eating less than wanted (so-called hedonic hunger) rather than less than needed. Using fMRI, a pilot study found numerous differences in brain activation of normal weight REs and unrestrained eaters (UREs) in response to highly palatable food stimuli in a fasted or fed state. The current study aimed to replicate these findings with a larger number of subjects. In a within-subject design, brain activation of normal weight REs (N = 9) and UREs (N = 10) was studied when in a fasted and fed state and when viewing pictures of highly and moderately palatable food. UREs showed widespread bilateral activation to high palatability food stimuli when fasted, in areas associated with hunger, memory, and motivation. In the same state REs showed virtually no activation that survived statistical threshold. While viewing high palatability foods in a fed state, REs showed activation in areas associated with goal-oriented planning, expectation of reward and goal-defined behavior (left orbitofrontal cortex and dorsolateral prefrontal cortex), and food craving and desire (left insular cortex). Activation for UREs under the same conditions was found in areas related to satiation and memory. These findings support results from the preliminary study and suggest that: 1) when food deprived, REs eat relatively little not because they are dieting but because they are less motivated to eat, and 2) consumption of a filling meal by REs paradoxically increases the reward value of palatable food (i.e., creates a state of hedonic hunger).
PALATABLE, HIGH FAT DIET AMELIORATES ANXIETY-LIKE BEHAVIOR INDUCED BY MATERNAL SEPARATION IN MALE RATS . ; Pharmacology, School of Medical Sciences, University of New South Wales
Postnatal maternal separation (MS) is a well-studied model of early life stress that
leads to long-term changes in offspring stress responsiveness. In the present
study we investigated whether the effect of MS on subsequent anxiety-like
behavior was modulated by provision of a palatable, varied, high fat (HF) diet.
Young adult Sprague-Dawley rats (13 weeks) were mated and dams were randomly assigned to either MS180 (3 hours), MS15 (15 minutes/day) or Non-Handled (NH) from
postnatal days (PND) 2-14. Rats were weaned at PND 20 and assigned either chow
or HF diet. Anxiety-like behavior was assessed using elevated plus maze at 11
weeks of age. 24 h food intake was monitored weekly.
At 11 weeks, male MS180 and NH rats spent less time in the open arms (39.3±3.39; 15.9± 3.8 % time) relative to MS15 (62.7± 5.1%), but only in the chow fed animals (F=
5.054, p<0.001). Interestingly, this was reversed by giving MS180 and NH
rats access to HF diet. Plasma leptin in MS15 rats was elevated compared to
MS180 rats consuming the same diet. MS15 rats consuming chow were significantly
heavier (490.2±12.4g, p<0.05) compared to MS180 (435.6±8.3g) and NH (452.0±15.6g)
rats. This difference was not present in the HF groups. In our hands mothers of MS180 rats also showed increased anxiety-like behaviour. As previously
shown, early life stress resulted in increased anxiety-like behavior, and a
short separation was protective. Our data suggest that voluntary consumption of
HF diet may act as a natural reinforcer in reducing anxiety-like behaviour
after early life stress, perhaps due to its palatability.
MERCAPTOACETATE (MA) STIMULATES FEEDING AFTER INFUSION INTO THE HEPATIC PORTAL VEIN (HPV) OR VENA CAVA (VC), BUT NOT AFTER INFUSION INTO THE DESCENDING AORTA. ; Institute of Animal Sciences, ETH Zurich
Intraperitoneal injections of mercaptoacetate (MA) inhibit hepatic fatty acid oxidation and stimulate feeding. Abdominal vagal afferents mediate the feeding-stimulatory effect of MA, but it is unclear where in the abdomen this effect originates. We addressed this question by assessing the feeding-stimulatory effects of MA infusions into the hepatic portal vein (HPV), the vena cava (VC), and the descending aorta near the beginning of the celiac artery (NCA). In separate experiments, ad lib-fed male Sprague-Dawley rats (> 400 g body weight (BW)) received HPV, VC, or HPV vs. NCA infusions (40 µl/min) of MA (45.6 mg/kg; 15 mM) or saline in the middle of the light phase. Food intake was measured for 12 h. MA stimulated feeding similarly after HPV and VC infusions, but had not effect on feeding after NCA infusion. To our knowledge, this is the first report of a stimulation of feeding after intravenous MA infusion in rats. The data do not disclose the origin of MA’s feeding-stimulatory effect, but suggest that MA does not increase food intake by acting either in the liver or in the intestine.
HYPERPHAGIA-INDUCED OBESITY IN YOUNG MALE AND FEMALE OLETF RATS: A DEVELOPMENTAL STUDY. ; 1Bar-Ilan Univ, 2Johns Hopkins Univ
OLETF rats lack the expression of functional CCK1 receptors and are a model of hyperphagia-induced obesity used to study the early origins and neurobiology of obesity. OLETF pups are heavier than LETO controls from birth and develop pre-obese characteristics early in life. In the present study, we aimed to examine the development of young males and females towards obesity. Rats were weighed every fifth day from the time of weaning, intake was assessed daily and feeding efficiency was calculated. Animals were sacrificed at 4 different time-points: weaning (postnatal day [PND] 22), PND 38, 65 and 90. Blood plasma was collected for leptin analysis. Brown, retroperitoneal, inguinal and epididymal fat pads were collected and weighed. Adipocyte cell size was assessed from the inguinal fat pad. The estrous cycle of the females was monitored from PND 40 until PND75. Patterns of intake and sugar preference were measured at critical times. Results show pre-obese characteristics in the OLETF strain since childhood and appear to show a specific time-point at PND 65 where obesity sharply increases. The high and sudden accumulation of white fats observed here in both sexes are accompanied by hypertrophic adipocyte development and very high leptin levels. While intake was about 30-40% higher in the OLETF strain, the feeding efficiency did not differ between the strains, further suggesting that obesity in this strain develops following life-long abnormalities in eating behavior and not as a consequence of a metabolic disorder.
[Support: US-Israel BSF]
VISCOSITY AND SWEET TASTE AS DETERMINANTS OF CALORIC COMPENSATION IN RATS . ; Department of Psychological Sciences and the Ingestive Behavior Research Center, Purdue University
Energy and weight regulation depend, in part, on an animal’s ability to compensate for excess calories consumed on one occasion by decreasing energy intake at another time. Recent research suggests that this type of caloric compensation may be strongly influenced by the orosensory properties of foods. For example, compensation is usually weaker following consumption of low viscosity than high viscosity foods. Similarly, rats exposed to sweet taste paired occasionally without calories eat more food after consuming a sweet, high calorie premeal than rats only exposed to sweet taste paired with calories. Thus, both viscosity and sweet taste can influence compensatory ability when tested separately. However, it is unknown how these cues determine compensation when both are presented simultaneously. We investigated this interaction using adult, male Sprague-Dawley rats in a standard preload test paradigm. Animals received 10 gram, equicaloric, premeals that factorially combined high and low viscosity with sweet and bland taste, and amount of lab chow eaten during a subsequent test meal was measured. Weaker caloric compensation was found following low compared to high viscosity premeals independent of sweet taste. A follow up study that manipulated prior experience with sweet taste, viscosity, and calories did not abolish the effects of viscosity on caloric compensation. These data suggest that the effects of viscosity on caloric compensation may occur independently of variations in sweet taste.
BLOCKING OF BRANCH CHAIN AMINO ACID METABOLISM DECREASES HYPOTHALAMIC POMC AND INCREASES AGRP EXPRESSION IN MICE ON A LOW FAT DIET. ; 1Pennington Biomedical Research Center, 2LSU AgCenter, 3Wake Forest
High protein diets lower the expression of AGRP and suppress appetite. In addition, the branch chain amino acid, leucine acts locally within the hypothalamus to regulate hypothalamic neuropeptide expression and feeding behavior. Nonetheless, the role of branched-chain amino acid metabolism in this signaling remains unclear. To further investigate the role of BCAA metabolism in neuronal function, we utilized mice deficient for BCATm, which is the enzyme catalyzing the first step in peripheral BCAA metabolism. BCATm−/− mice exhibit elevated plasma leucine and reduced adiposity and body weight despite eating more food, along with increased energy expenditure. The wild type and knock out mice were fed either a high fat or a low fat diet to determine if the lack of leucine metabolism would alter the response to a high fat diet. Arcuate nucleus (ARC) micropunches were collected for five continuous coronal sections, and levels of agouti-related protein (AgRP), neuropeptide Y (NPY) and proopiomelanocortin (POMC) mRNA in the ARC were determined using real-time reverse transcriptase polymerase chain reaction. Compared with wildtype mice, POMC expression was significantly decreased and AgRP expression increased in the arcuate nucleus of BCATm−/− mice (p<0.05) on the low fat diet but not on mice receiving the high fat diet. It is proposed that the high fat diet increased the levels of leptin in the KO mice and reversed the effects of low leucine utilization on neuropeptide expression.
CANNABINOID CB1 RECEPTOR ANTAGONIST AM251 REDUCES PALATABLE DESSERT CONSUMPTION AND BODY WEIGHT GAIN IN FEMALE C57B6 MICE. . ; Department of Psychology, University of Florida
Taste-reactivity and brief-access tests support the hypothesis that the hypophagic effect of cannabinoid CB1 receptor antagonists results from their effect on the perception of palatability. The effect of CB1 antagonists on consumption of and preference among more complete food types in rodents has been less thoroughly explored. We have previously reported a dessert protocol that models overconsumption in which female rats given access to a high calorie preferred diet consumed more calories than rats given no dessert or rats given a low calorie preferred diet. We have also shown that rats on this dessert protocol that are injected daily with CB1 antagonists Rimonabant or AM251 reduce caloric intake compared to vehicle injected controls. Interestingly, the decrease in caloric intake is specific to the dessert. In the present study, we generalize this protocol to female mice. Female C57B6 mice were given ad libitum access to moist chow (1.67 kcal/g) and 8 h nocturnal access to a sugar fat whip dessert (SFW, 2 parts vegetable shortening + 1 part sugar, 7.35 kcal/g) daily for two weeks. Mice were also injected daily with either one of three doses of AM251 (1, 3, or 10 mg/kg IP) or vehicle (equal parts polyethylene glycol and saline 1 ml/kg). Mice injected with AM251 ate fewer total calories and gained less weight than mice injected with vehicle. However, unlike our previous report using rats, this was not specific to the dessert. This suggests a species difference in diet preference and/or how AM251 affects diet selection. Support via DK064712.
ESTABLISHMENT OF PREFERENCE FOR FLAVOR PAIRED WITH INTRAGASTRIC GLUCOSE, BUT NOT WITH INTRAVENOUS NICOTINE OR COCAINE. . ; Department of Psychology, University of Florida
This study compared the relative dependency of nutrient and drug reward on associated taste cues. Sclafani et al (1988, 1993) have reported a strong preference for tastes that are temporally paired with intragastric (IG) glucose. We replicated this phenomenon and attempted to generalize it to tastes paired with intravenous (IV) nicotine and cocaine. Rats were divided into groups based on licks of saccharin solution (1% in dH20) in acclimation sessions and surgically implanted with chronic indwelling IG or IV catheters. After recovery, rats were run for 6 days in 50 min sessions in operant chambers equipped with a retractable spout and in which the rats were attached to a swivel line connected to a pump-driven syringe. On odd days, the spout contained either a cherry or grape Koolade-flavored saccharin solution that was designated the CS+, and licking this solution resulted in brief infusion of a reinforcer: glucose (8%), nicotine (0.4 mg/kg), or cocaine (6.25 mg/kg). On even days, the other flavor (the CS-) was presented, and saline infusion was contingent on licking. On the seventh day, both flavors were presented and licking resulted in no consequence. Robust preference for the flavor associated with IG glucose was seen, but no distinct preference or aversion was seen for flavors paired with nicotine or cocaine. This suggests that flavor may not be a sufficient cue to signal drug reward and supports the hypothesis that there are distinct mechanisms by which drug and nutrient reward are processed. Support via DA019288.
INVESTIGATION OF OSMOREGULATORY AND HYPOVOLEMIC THIRST MECHANISMS IN MICE LACKING ANGIOTENSINOGEN. ; 1Howard Florey Institute, Univ. of Melbourne, 2Dept. of Physiology, Univ. of Melbourne, 3St Vincent's Institute of Medical Research and Dept. of Medicine, Univ. of Melbourne,, 4Dept. of Physiology, Monash Univ.
Water intake in response to hypertonicity, hypovolemia and dehydration was investigated in mice lacking angiotensin II as a result of deletion of the angiotensinogen gene (Agt-/- mice), and in wild-type mice (WT-mice). Daily water intake in Agt-/- mice was approximately threefold that of WT-mice due to increased urine losses in Agt-/- mice. Intraperitoneal (i.p.) injection of hypertonic saline caused a similar dose-dependent increase in water intake in both Agt-/- and WT-mice. Agt-/- mice drank appropriate volumes of water following water deprivation, however, Agt-/- mice did not increase water or 0.3 mol/l NaCl intake in response to a hypovolemic stimulus (s.c. polyethylene glycol) but WT-mice did so. Osmoregulatory regions of the brain (supraoptic and paraventricular nuclei and lamina terminalis) showed increased number of neurons expressing Fos in response to i.p. hypertonic NaCl in both Agt-/- mice and WT-mice. Hypovolemia increased Fos expression in the lamina terminalis and supraoptic nucleus in WT-mice, but not in the lamina terminalis in Agt-/- mice. These data show that brain angiotensin is not essential for the neural pathways mediating osmoregulatory thirst. Angiotensin of either peripheral or central origin is necessary for hypovolemic thirst and salt appetite.
'FUNCTIONAL' FOOD INGREDIENTS FOR APPETITE CONTROL: CURRENT STATUS AND ISSUES. ; Unilever Food and Health Research Institute, Unilever R&D Vlaardingen
Food manufacturers and ingredient suppliers are increasingly directing their R&D activities toward building and substantiating stronger claims relating to weight control benefits. Most existing and emerging commercial food-based approaches to weight control focus on energy intake, primarily with technologies to achieve a low or reduced energy content of products. More recently, greater effort has been directed toward establishing and enhancing the added, ‘functional’ effects of ingredients and products on satiety and food intake. The physiological targets for food-based enhancement of appetite control are mostly gastrointestinal mechanisms, but range from sensory stimulation to post-absorptive metabolic, hormonal or neural actions. Several proposed ‘functional’ ingredients and approaches will be described. The quality and quantity of supporting evidence for proposed food ‘functional’ agents varies greatly, and the different standards and evidence used to support appetite control claims is a difficult and increasingly problematic issue. Companies with higher scientific standards find themselves undermined by borderline claims and less scrupulous operators. This is not just an issue for industry: Arguably, the academic community has not become sufficiently involved in the scrutiny of ‘functional’ food research and claim substantiation. The ability to use specific ingredients is, however, not only determined by efficacy, but is also tremendously influenced by factors such as supply chain, processing, food quality, regulatory, consumer and marketing considerations.
FUNCTIONAL FOOD INGREDIENTS FOR APPETITE CONTROL: CURRENT STATUS AND ISSUES . ; Unilever Food and Health Research Institute
Food manufacturers and ingredient suppliers are increasingly directing their R&D activities toward building and substantiating stronger claims relating to weight control benefits. Most existing and emerging commercial food-based approaches to weight control focus on energy intake, primarily with technologies to achieve a low or reduced energy content. More recently, greater effort has been directed toward establishing and enhancing added, ‘functional’ effects on satiety and food intake. The physiological targets for food-based enhancement of appetite control are mostly gastrointestinal mechanisms, but range from sensory stimulation to post-absorptive metabolic, hormonal or neural actions. Several proposed ‘functional’ ingredients and approaches will be described. Most success has come through selective use of established ingredients (e.g. specific fibres and proteins). However, the quality and quantity of supporting evidence for these and proposed food ‘functional’ agents varies greatly, and the different standards and evidence used to support appetite control claims is an increasingly problematic issue. Companies with higher scientific standards find themselves undermined by borderline claims and less scrupulous operators. This is not just an issue for industry: Arguably, the academic community should become more self-critical and active in the scrutiny of ‘functional’ food research and claim substantiation. In addition, the ability to use specific ingredients is not solely determined by efficacy, but tremendously influenced by economic, supply chain, processing, food quality, regulatory, consumer and marketing considerations.
WHAT HAPPENS IN OUR BRAIN WHEN WE GET READY FOR DINNER? . ; Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht
Energy balance is regulated in a homeostatic manner by the hypothalamus,
which receives metabolic input from the body. Corticolimbic structures receive other relevant information such as the rewarding aspects of food and serve as a non-homeostatic control, which can override the hypothalamus.
We hypothesize that the imbalance of energy intake and energy expenditure seen in people with eating disorders is caused by interference of these structures, which drive the motivational control of energy balance. Rats develop anticipatory behaviour in expectance of food, which is suggested to reflect the drive to eat. Furthermore, c-fos studies showed
the involvement of several brain areas in food anticipation. Which neuronal
populations drive food anticipation is however not known yet.
The aim of this study is, therefore, to identify the neural and molecular substrates of anticipation to food and their involvement in potentiation of over-consumption.
Rats subjected to either a restricted feeding schedule or a palatable feeding
schedule showed clear anticipation to the meal. Studies are on the way to identify
brain areas and neuronal populations that exhibit c-fos just before meal-time. These studies aim to unravel the role of different brain areas and neuropeptides in anticipatory behaviour before highly palatable food is available.
ACUTE LOW-DOSE I.P. AMYLIN + EB TREATMENT IN OVX RATS DOES NOT PRODUCE AN ENHANCED ANOREXIGENIC RESPONSE.. ; Prog. in Neuroscience and Dept. of Biomedical Sci.
Amylin (AM) decreases food intake after both peripheral and central administration by reducing meal size. Estradiol is an indirect control of meal size and it enhances the hypophagic effect of several anorexigenic compounds. Estrogen and AM receptors are located in many of the same brain regions that influence feeding. The goal of this study was to determine if estradiol enhances the anorexigenic effect of AM. Eight ovariectomized Long-Evans rats underwent 4 cycles of hormone treatment during which they received β-estradiol 3-benzoate (EB, 4μg, s.c.) for 2 cycles and oil for 2 cycles. On the 4th day of each cycle, food/water were removed ~45 min prior to dark and AM (5μg/kg BW, i.p.) or saline was injected. At dark onset, food/water were made freely available and weighed hourly for 4 h and at 24 h. EB rats ate less than oil rats at all time points, regardless of drug treatment (p<.05). Surprisingly, AM did not produce a decrease in food intake in oil rats (cumulative food intake at 4 h and 24 h: OIL-sal= 7.1 ± 0.8g, 23.6 ± 0.8g; OIL-AM=6.5 ± 0.7g, 22.6 ± 1.1g). By 4 h, EB-AM rats showed a trend toward less food intake (3.5 ± 0.5g) than EB-sal (4.5 ± 0.7g) rats, but this difference was not significant. The results indicate that at this dose, peripheral AM does not: 1.) reduce food intake in OVX females, despite being effective in males, nor 2.) produce a synergistic effect with EB. Support: NIH F31 NS057856-01.
THE EFFECT OF GHRELIN ON FOOD AND WATER INTAKE DURING OSMOREGULATORY CHALLENGES. ; Department of Psychology, University at Buffalo
Ghrelin has been studied extensively in the context of feeding behavior, but less is known about its influence on water intake. A recent study demonstrated that ghrelin reduced drinking in rats after water deprivation. To further explore the anti-dipsogenic actions of ghrelin, we investigated the effects of this orexigenic peptide on both food and water intake under several dipsogenic conditions. Specifically, animals were exposed to one of five conditions that each lead to increased water intake: 24 hr water deprivation, replacing drinking water with 2.5% NaCl for 24 hr, injection of hypertonic saline, injection of angiotensin II (AngII), or the combination of hypertonic saline and AngII. Animals in each condition were injected with vehicle or ghrelin and subsequent food and water intakes were measured. Ghrelin reliably increased food intake in each condition, but the effects of ghrelin on water intake were less consistent. Ghrelin had anti-dipsogenic effects in animals given AngII or hypertonic saline injections, but failed to attenuate drinking in the more chronic conditions or when AngII and hypertonic saline were given together. The observed differences in the anti-dipsetic effect of ghrelin under the stimulus conditions may be due to an inability of the peptide to inhibit water intake when motivation to drink is high. These experiments demonstrate that ghrelin has anti-dipsogenic effects under some conditions, but the specific nature of the effect requires further clarification.
EGM is supported by a SUNY at Buffalo Presidential Fellowship. Additional support from NIH award DK73800 to DD.
BEHAVIOURAL MARKERS OF THE PRE-OBESE PHENOTYPE IN CHILDREN: WHAT PREDICTS WEIGHT GAIN?. ; Glasgow Caledonian University
Poor intake regulation and over consumption of palatable foods may characterize the pre-obese phenotype in children. Compensation index (COMPX) indicates the capacity of children to adjust intake in response to a preload and eating in the absence of hunger (EAH) reflects inability to resist eating. Three experiments were conducted to investigate the stability of these behaviours; to assess the role of learning in intake control and to determine their impact on weight change. In Experiment 1 COMPX was measured in 33 3-5 yr old children in response to a low (LE) or high (HE) energy beverage at T1 then repeated at T2 (2 weeks later). Children adjusted intake of a test meal in response to the preloads (COMPX = 82 + 19.2%, 61+ 15.5%), but these were not correlated. Experiment 2 measured COMPX and EAH over 7 months in 28 3-5 yr old children. Again correlations between COMPX scores were weak but EAH scores were significantly correlated [r (14) = 0.58, p <0.01] and predicted weight gain [r (17) =0.83, p <0.0001]. Experiment 3 was conducted to examine the role of learning by providing 25 4-5 yr old children the same LE or HE beverage each day for 10 days. Test meal intake was measured at T1 and T10. Children decreased test meal energy intake in response to the preloads and decreased weight of food consumed with repeated exposure. Overall, these findings suggest that EAH is a stable attribute and predicts weight gain, in contrast to COMPX.
EFFECT OF PRENATAL AND/OR POSTNATAL HIGH FAT DIET ON GLUCOSE HANDLING, FOOD CONSUMPTION AND MOTIVATION IN BORDERLINE HYPERTENSIVE RATS (BHR) . ; University of Florida
The aim of this study was to determine whether maternal over-nutrition produces obesity, hyperphagia or impaired glucose tolerance in rats with a genetic predisposition to mild hypertension. Adult female Wistar rats were maintained on either high-fat (HF: 60% lard) or low fat (LF: 10%) semipurified diets for 8 weeks, after which they were mated with male spontaneously hypertensive rats (SHR). Gestating females were maintained on the same diets as prior to impregnation. At parturition, the BHR litters were culled to 6M+4F pups (only the females were used in this study) and were cross-fostered to a dam with either the same or the alternate diet as their biological mother, thus forming four groups. At weaning, half the females from each litter were fed Purina chow while the other half were placed on a varied HF cafeteria diet for the remainder of the experiment. Body weight and food intake were monitored every 2 days. At PD 200 the rats were fasted for 18 h and then an oral glucose (2 g/kg) tolerance test was administered. After this, the rats were tested in an operant paradigm to examine for differences in motivation to obtain a palatable food. Preliminary results indicate that body weight does not differ significantly between conditions but total fat pad mass is significantly greater in the rats maintained on the postweaning high-fat diets, and these rats have poorer glucose tolerance. Gestational and preweaning diet condition had little effect. Rats on high and low fat diets showed similar food procurement in the motivational protocol.
ISOCALORIC VERSUS HYPERCALORIC FAT INTAKE: DIFFERENTIAL IMPACT ON HYPOTHALAMIC NPY, POMC, GLUCOSE TOLERANCE AND ADIPOSITY IN THE RAT. ; Pharmacology, School of Medical Sciences, University of New South Wales
The effect of macronutrient composition of the diet on hypothalamic appetite
regulatory pathways and the development of obesity is controversial. We
investigated the impact of increased dietary fat, under isocaloric and
hypercaloric conditions, on adiposity, metabolism, and brain appetite
regulators, NPY and POMC. Six week old male Sprague-Dawley rats were exposed to
Control (CON, 14% fat), high-fat restricted diet (HFD-R, high-fat palatable
diet, matched to energy intake of control), or ad libitum high-fat palatable
diet (HFD, 33% fat). Body weight and food intake were monitored
throughout. Rats were killed under fasting conditions at 11 weeks.
Energy intakes at 11 weeks were 306+11, 317+0.1 and 846+55
kJ/rat/day in CON, HFD-R and HFD rats respectively. Pair-fed HFD-R animals had
doubled fat mass (P<0.01) and elevated plasma leptin, insulin and
triglycerides (P<0.05), with more marked increases in the HFD rats. Animals
fed ad libitum HFD had significantly increased caloric intake, body weight and
fat mass (P<0.001), hyperleptinemia and hyperinsulinemia.
Total fat mass remained elevated in HFD-R and HFD after correction for body weight
(4.5, 7.1 and 10.6% body weight in CON, HFD-R and HFD respectively. Animals consuming unlimited HFD had more than a doubling of NPY mRNA, possibly reflecting increased hunger under fasting conditions, with more modest increases in POMC mRNA, in the ventral hypothalamus. Although isocaloric high-fat diet had no impact on hypothalamic appetite regulators or body weight, adiposity was increased, suggesting that the proportion of dietary fat, independent of caloric intake, affects fat
deposition and metabolic profile. The unrestricted palatable diet induced
greater physiological and neuroendocrine responses, highlighting the powerful
effects of hedonic overeating.
CHARACTERIZATION OF THE BLOOD-BRAIN BARRIER AT THE MEDIAN EMINENCE OF THE HYPOTHALAMUS: A ROLE FOR TANYCYTES IN REGULATING ACCESS OF PERIPHERAL HORMONES TO THE ARCUATE NUCLEUS? . ; 1Inserm U837, 2The Saban Research Insitute
The arcuate nucleus of the hypothalamus (ARH) is a critical component of the neural pathways that regulate energy balance and it plays a key role in relaying leptin signals to other parts of the brain. However, how peripheral signals reach the ARH to mediate their central effects is largely unknown. The median eminence (ME) is located adjacent to the ARH. The ME contains a rich fenestrated capillary plexus making the ME a direct target for blood-borne molecules. In the ME, there are specialized ependymal cells, named tanycytes, which have been postulated to harbour properties of barrier cells, preventing substances contained into the portal vessels from entering the brain. In our study, immunohistochemistry was performed to examine the expression of tight junction proteins in the ME in mice. The results show that tanycytes express occludin, ZO-1, claudin 1 and 5. Interestingly, in tanycytes that line the ventral part of the third ventricle, these molecules are organized as a continuous belt around the cell bodies. In contrast, in tanycytes dorsal to the ME, these proteins exhibit an unorganized pattern of expression. Evans Blue dye was used to study further on permeability in this region. Only tanycytes located at the level of the ARH showed permeability to the dye. Together, these data suggest that tanycytes located in the ME may have important function as barrier cells, thereby regulating the transport of hormones from the periphery to the brain.
A HIGH FAT DIET MODIFIES FOOD INTAKE, VAGAL AFFERENT SENSITIVITY TO CHOLECYSTOKININ (CCK) AND MRNA PROFILE OF GUT MEDIATOR RECEPTORS IN VAGAL NEURONS. . ; UMR 914 ,INRA/AGROPARISTECH
During digestion, macronutrients are sensed within the small intestine. This sensory process is dependent up on gut mediator action, such as cholecystokinin (CCK) or serotonin (5HT), on vagal afferents that in turn, convey peripheral information to the brain in order to influence the control of food intake. Recent studies have suggested that dietary conditions alter vagal sensitivity to CCK and 5HT. This phenomenon may be of importance in the onset of eating disorders. The aim of the present study was to investigate the effect of a high-fat diet (HF:30% fat, 54% carbohydrate) or a high-carbohydrate diet (HC:10% fat, 74% carbohydrate) on food intake, vagal sensitivity and vagal afferent neurons receptor profiles in mice fed for 15 days. After diet , mice were tested for: (i) amplitude of the inhibitory effects of CCK and 5HT on short term food intake through behavioural measurements, (ii) NTS responsivity to intragrastric macronutrient loads and anorectic gut mediators (CCK and 5HT) using c fos immunostaining as a marker of neuronal activation; and (iii) nodose ganglia (vagal afferent neuron cell bodies) receptors transcript levels using quantitative PCR. Results indicated that, compared to a high carb diet, a high fat diet alters short term response to CCK and intragastric macronutrient loads while decreasing vagal activation by CCK and modifying receptor expression on vagal neurons.
OREXIN A-INDUCED ACTIVITY IS INVERSELY CORRELATED WITH BODY WEIGHT GAIN AND MAY PROMOTE WEIGHT LOSS IN RATS. ; 1University of Minnesota, 2Veterans Administration Medical Center
Studies in humans and animals suggest that high levels of spontaneous physical activity (SPA) protect against weight gain. We are investigating whether orexin A (OXA) influences body weight by contributing to SPA levels in rodents. We hypothesized that (1) OXA responsiveness and OX receptor expression are correlated to SPA and body weight gain, and (2) that OXA injections would increase SPA and reduce body weight gain. To test this, adult male rats were treated with OXA via guide cannulae aimed at the rostral lateral hypothalamus. For experiment 1, we measured 2 hour SPA following a single OXA injection (31.25 pmol). Body weights were monitored for 6 weeks post-treatment. Body weight gain over this period was significantly and inversely correlated to levels of OXA-induced SPA (R2=0.435, p=0.038), and to orexin 2 receptor expression in the rostral lateral hypothalamus (R2=0.686, p=0.0260). For experiment 2, rats were treated three times daily with OXA (500 pmol) or artificial cerebrospinal fluid (aCSF) for five days. OXA treatment significantly increased dark-period SPA in one group (p<0.05). A second group receiving OXA showed weight loss (OXA: -32.8±15.0 g; aCSF: -7.6±8.4 g; p=0.18), but the effect did not reach significance. We attribute this to the short duration and small animal numbers in this pilot study; a more extensive follow-up study is planned. These data suggest that OXA sensitivity and receptor expression level may predict body weight gain, and that OXA therapy elevates SPA and may reduce body weight.
SUPPRESSED INTAKE OF HIGHLY PALATABLE FOOD AND DYSFUNCTION OF THE HPA AXIS ACTIVITY RESPONDING TO RESTRAINT STRESS IN ADOLESCENT RATS THAT EXPERIENCED NEONATAL MATERNAL SEPARATION. ; Dental Research Institute, Department of Biochemistry, Department of Oral & Maxillofacial Surgery, Seoul National University School of Dentistry
Repeated maternal separation during pre-weaning period leads to permanent alterations in characteristics of the hypothalamic-pituitary-adrenal gland (HPA) axis activity in rats later in life. This study was conducted to examine the HPA axis activity responding to stress challenges at adolescence in rats that experienced maternal separation repeatedly during neonatal period. Sprague-Dawley pups were separated from dam daily for 3h during PND 1 - 14 (MS) or left undisturbed (NH). After weaning on PND 22, male pups were singly caged with ad libitum access to standard chow and water. All pups were subjected to a preference test with free choices of chow or chocolate cookie for 1 h every alternate day from PND 28, with(RR)/without(NR) 1 h of restraint stress prior to the test. All pups were perfused with 4 % PFA on PND 40; RR pups immediately after the restraint session; and a half of NR pups after a single restraint. Cardiac bloods were collected for corticosterone assay and the brain tissues were processed for c-Fos immunohistochemistry in the hypothalamic paraventricular nucleus (PVN), the central nucleus of amygdala (CeA) and the nucleus accumbens of striatum (NAccb). Body weight gain of MS pups tended to be decreased without statistical significances, compared to NH pups. Repeated restraint did not affect weight gain of NH nor MS pups. Cookie intake was significantly suppressed in MS pups compared with NH pups. Restraint stress suppressed cookie intake of NH pups, but not of MS pups. Restraint stress significantly increased c-Fos expression in the NAccb of NH pups, but not in MS pups. Furthermore, c-Fos-ir in the NAccb core of MS pups increased significantly, compared to NH pups. c-Fos expression in the PVN of MS pups responding to restraint stress did not significantly differ from NH pups. However, basal c-Fos expression in the CeA of MS pups increased significantly, compared to NH pups. The CeA-c-Fos was markedly increased by single restraint in NH pups, but not in MS pups. Basal plasma level of corticosterone was elevated in MS pups compared with NH pups. A single restraint increased plasma level of corticosterone both in NH and MS pups, but the repeated restraint only in NH pups. These results suggest that experience of neonatal maternal separation may suppress intake of highly palatable food (a pleasure seeking behavior) in rats at adolescence, perhaps, due to dysfunction of the HPA axis. Supported by KMOST & MOEHRD (JWJ)
THE EFFECTS OF MODIFIED SHAM FEEDING AND VARIETY ON SENSORY SPECIFIC SATIETY AND FOOD INTAKE IN HUMANS.. ; 1Department of Psychology, Wagner College, 2Department of Psychology, Glasgow Caledonian University
Sensory specific satiety (SSS) occurs in the absence of postingestive feedback via use of a modified sham feeding procedure (MSF). MSF increases satiety and fullness ratings; gut humoral events associated with hunger and satiety are initiated by MSF. In the present experiment, less suppression of food intake after MSF than after eating was predicted since there is no postingestive feedback. Furthermore, since variety tends to increase food intake, it was hypothesized that SSS to one food would suppress intake of the same food in a subsequent meal compared to intake of a different food. 23 participants (16 women, 7 men) from the US and UK ate lunch on four occasions in the laboratory in a repeated measures design with MSF (sham feed or eat in first course) and food variety (same or varied sandwich in second course) as factors. SSS was tested before and after each course. The first course was cheese sandwiches; the second was either cheese (same) or ham (varied) sandwiches. In the first course, there were no differences in intake among the conditions. Participants ate fewer sandwich units in the second course after eating than after MSF [F(1,21)=22.72 , p<0.001]. Participants ate more in the varied than in the same condition [F(1,21)=11.40, p<0.01]. There was no difference in SSS to cheese for MSF and eating conditions. Thus, the pleasantness of the taste of the eaten food declined whether that food was sham fed or eaten [F(5,110)=20.32, p<0.001]. There was no interaction between MSF and variety conditions on food intake. Hunger ratings decreased after eating but not after MSF. The results suggest that while MSF can produce SSS, it does not lower food intake. Thus, sensory specific satiation is important in limiting food intake only when coupled with the relevant negative postingestive feedback.
CONDITIONED TASTE AVERSION AND NA-APPETITE AFTER ASYMMETRIC BRAIN LESIONS.. ; 1Penn State Univ., 2Univ. of Louisville
In rodents, the central gustatory system has monosynaptic projections from the pontine parabrachial nuclei (PBN) that distribute widely in the limbic forebrain. Unlike its thalamocortical counterpart, this ventral gustatory pathway is largely unilateral. Bilateral damage to the PBN eliminates the ability of rats to acquire conditioned taste aversions (CTA) or to exhibit Na-appetite (Na-Ap). Damage to the thalamic taste area has little effect on either of these taste guided behaviors. Thus, a lesion of the PBN on one side and damage to one of its limbic targets on the other should reveal if interaction between the two structures supports either CTA or Na-Ap. Experiments using this strategy demonstrated that, although the PBN is critical for both behaviors, connections with the lateral hypothalamus (LH) and the central nucleus of the amygdala (CNA) contribute differently to their elaboration. Asymmetric lesions of the PBN and the CNA failed to block a CTA but they increased the initial intake of a sucrose CS and considerably sped up extinction. Rats with bilateral CNA damage also displayed exaggerated CS intake on trial 1, but exhibited little if any extinction of a CTA. In the same 2 sets of animals both the induced Na-Ap and need-free NaCl intake were increased. Asymmetric lesions of the PBN and the LH slowed acquisition of a CTA and sped up its extinction. In the same PBN/LH rats, however, Na-Ap was essentially eliminated. Prelesion experience with Na-Ap protected PBN/LH rats from the deficits in stimulated salt intake. Support: NIH DC0240, DC05435, DC08937.
HIGH-SUGAR AND HIGH-FAT DIETS: DIFFERENTIAL EFFECTS ON EXPRESSION OF GENES INVOLVED IN REWARD AND SATIETY. ; 1Minnesota Obesity Center, 2Department of Neuroscience, Uppsala University, 3Department of Food Science and Nutrition, University of Minnesota
Consumption of palatable high-sugar and high-fat diets exceeds levels necessary to satisfy energy needs of the organism. It remains unclear whether overconsumption of diets rich in sugar versus those high in fat relies on different central mechanisms. By employing real-time PCR, we found that ad libitum 48-h consumption of 10% sucrose or 5% Intralipid solution in mice led to an increase of hypothalamic kappa and mu opioid receptor mRNA expression, whereas activity of genes that give rise to opioid peptides remained unchanged. Expression of orexigenic genes involved in energy homeostasis, including neuropeptide Y, melanin concentrating hormone and orexin was not affected. Interestingly, intake of the sucrose diet blunted expression of a satiety mediator, oxytocin, whereas Intralipid intake had no effect. Neither of the two diets affected mRNA levels for CRH, CCK or CART. We conclude that high-sugar and high fat diets similarly increase activity of the opioid reward system, however, only sucrose-rich tastants decrease satiety signaling provided by oxytocin.
FTO GENE IN THE MOUSE BRAIN: DISTRIBUTION AND LINKS WITH FEEDING CONTROL. ; 1Minnesota Obesity Center, 2Department of Neuroscience, Uppsala University, 3Department of Food Science and Nutrition, University of Minnesota
Recent human population studies have associated gene variants of the FTO (fatso) gene with BMI and obesity. Animal experiments performed to date have shown that this gene is highly expressed in the brain and an energy status of the organism affects its expression. In the current project, we employed in situ hybridization methodology and examined distribution of FTO mRNA in over thirty feeding-related central sites in the mouse CNS. FTO mRNA was found in multiple areas implicated in energy homeostasis as well as in those that govern reward processes, including the paraventricular, arcuate, dorsomedial, ventromedial and supraoptic nuclei in the hypothalamus, nucleus accumbens, central nucleus of the amygdala, dorsal vagal complex and bed nucleus of the stria terminalis. In addition, FTO was expressed in neurons synthesizing peptides involved in consumption control, including oxytocin and alpha-melanocyte-stimulating hormone. Finally, we exposed animals to various feeding regimens differing in diet composition and availability and – using real-time PCR methodology - found that hypothalamic FTO expression was affected not only by the energy status of the organism, but also by palatability of ingested food.
THE MICROTITER OPERANT GUSTOMETER (MOG): DEVELOPMENT OF A HIGH THROUGHPUT (HT) OPERANT TASTE DISCRIMINATION ASSAY. . ; Redpoint Bio
Taste discrimination is a behavioral paradigm that provides a direct quantification of an animal’s qualitative sensory experience. In operant taste discrimination, a specific taste cue indicates which of several behavioral responses will be rewarded. We describe a novel apparatus and methodology for a HT operant taste discrimination assay using rats. The MOG is a modified operant chamber in which rats sample taste stimuli by licking solutions, suspensions, or solids from a 96-well plate located beneath the floor. Single wells are accessed through an aperture in the floor. Each lick is detected by means of a laser-controlled switch that is activated as the tongue enters the well. Well-licking consequently produces two retractable levers from the front panel that operate a pellet dispenser. At the conclusion of a trial, the 96-well plate is advanced by an x-y motion table to align the next well with the aperture. Using the MOG, we have trained rats to discriminate 300 mM sucrose from water, quinine, citric acid, and NaCl. Rats sampled from all 96 wells to generate dose-response curves for 5 different nutritive and non-nutritive sweeteners within a 90 minute test session. Finally, rats tested 40 sweeteners from a variety of chemical classes demonstrating the capacity of the MOG as a HT primary screening apparatus. The MOG presents an enabling technology for rapid evaluation of large numbers of novel tastants or taste-modifying compounds with small sample volumes.
DECODING INSULIN ACTION ON THE OLFACTORY FUNCTION. ; UMR5020, CNRS/UCBL, 50 av. T. Garnier
Body weight is precisely controlled through a fine tuning of energy balance and appetite. Olfaction contributes to regulate food intake by modulating palatability. In turn, olfactory perception is influenced by metabolic and nutritional status. We have recently demonstrated that hungry rats smell better than satiated ones. We are interested in identifying the signals involved in the cross-talk between the pathways controlling feeding behavior and the olfactory system. Insulin is likely to be one of these signals, since the olfactory bulb (OB) is rich in insulin and insulin receptors (IR). Here, we characterize the action of insulin on the OB at cellular, tissue and behavioral levels. Immunohistochemical analysis shows that IR is localized in layers rich in synaptic contacts (glomerular, external plexiform and granular layers) and on the somas of the mitral cells (main neurons). ELISA quantification reveals that insulin is increased twofold in the OB of satiated versus fasted rats. Finally in behavioral studies designed to measure olfactory acuity, insulin has a dose dependent effect: at low dose, insulin increases olfactory detection, while at higher doses it decreases it. Patch clamp recordings of OB confirm this dual effect: insulin directly increases the spontaneous activity of the mitral cells or it decreases it. The decrease probably involves indirectly granular inhibitory interneurons. Altogether, this study provides converging evidence that insulin, by acting in the OB neural network, finely modulates olfactory activity in close relation with food intake.
DECODING INSULIN ACTION ON THE OLFACTORY FUNCTION. ; UCBL Lyon1 - CNRS UMR5020
Body weight is precisely controlled through a fine tuning of energy balance and appetite. Olfaction contributes to regulate food intake by modulating palatability. In turn, olfactory perception is influenced by metabolic and nutritional status. We have recently demonstrated that hungry rats smell better than satiated ones. We are interested in identifying the signals involved in the cross-talk between the pathways controlling feeding behavior and the olfactory system. Insulin is likely to be one of these signals, since the olfactory bulb (OB) is rich in insulin and insulin receptors (IR). Here, we characterize the action of insulin on the OB at cellular, tissue and behavioral levels. Immunohistochemical analysis shows that IR is localized in layers rich in synaptic contacts (glomerular, external plexiform and granular layers) and on the somas of the mitral cells (main neurons). ELISA quantification reveals that insulin is increased twofold in the OB of satiated versus fasted rats. Finally in behavioral studies designed to measure olfactory acuity, insulin has a dose dependent effect: at low dose, insulin increases olfactory detection, while at higher doses it decreases it. Patch clamp recordings of OB confirm this dual effect: insulin directly increases the spontaneous activity of the mitral cells or it decreases it, probably by indirectly involving inhibitory interneurons. Altogether, this study provides converging evidence that insulin, by acting in the OB neural network, finely modulates olfactory activity in close relation with food intake.
CALORIC RESTRICTION PRODUCES LONG-TERM CHANGES IN NEURAL PATHWAYS INVOLVED WITH STRESS AND REWARD. . ; University of Pennsylvania
“Yo-yo” dieting, common in weight management, is associated with an increased risk for long-term weight regain. We have shown previously that following three weeks of moderate caloric restriction, mice displayed heightened sensitivity to stress and increased depression-like behaviors. When re-fed on a palatable high fat diet, mice showed increased weight gain and caloric intake three months following the end of restriction. We hypothesize that the stress effects elicited by moderate caloric restriction produce long-term changes in stress and reward neurocircuitry enhancing intake of palatable foods. To mechanistically examine these effects, we analyzed gene expression patterns along the mesolimbic-striatal dopamine pathway after 75% caloric restriction. Measurement of changes in both reward and stress pathway components were assessed through taqman PCR of micropunches from specified brain regions. CRF in both the CeA and BNST showed significant alterations with caloric restriction. MCH and orexin were significantly decreased after caloric restriction, and did not return to baseline with re-feeding. We hypothesized that these persistent changes may be driven in part by epigenetic mechanisms. In the BNST, we found changes in CRF methylation consistent with gene expression. Together, these results suggest that the stress associated with moderate caloric restriction induces long-term changes in gene expression that may influence feeding behaviors. Examination of these pathways may enable development of more effective and lasting treatments for weight management.
THREE-WEEKS OF POST-WEANING EXERCISE IN DIO RATS FED HE DIET INCREASES CENTRAL LEPTIN SENSITIVITY AND HYPOTHALAMIC 125LEPTIN RECEPTOR BINDING. ; 1UMDNJ, Grad Sch Biomed Sci, 2Neuro Serv, VA Med Center
We hypothesized that post-weaning wheel running would prevent the development of obesity in diet-induced obese (DIO) rats fed a 31% high-energy (HE) diet. We previously showed that when 4wk old DIO rats were fed HE diet and exercised for 3wk (Ex3wk) post-weaning they gained 18% less weight and had 49% less adiposity than sedentary (Sed) rats 10wk post-exercise termination. We postulated the failure of ExSed rats to regain lost weight following exercise termination was due to an increase in central leptin sensitivity. Sed and Ex3wk DIO rats were injected with leptin (5mg/kg,i.p.) and hypothalamic pSTAT3 induction was assessed. Ex3wk rats showed 23% greater leptin-induced pSTAT3 immunoreactivity in the ARC compared to Sed animals. Ex3wk rats had an associated 36% decrease in baseline food intake (24hBase-18.55+0.8g;24hLep-11.88+1.1g;P=0.001) during the 24h period following leptin administration compared to Sed rats which did not reduce 24h intake. Rats that were Ex for 3wk and then allowed to remain Sed still had a 24% decrease in 24h intake (24hBase-26.62+1.0g;24hLep-20.12+1.4g;P=0.001) 4wk after exercise termination compared to Sed7wk rats which were insensitive to anorectic effects of leptin. Furthermore rats exercised for 3wk had a 95% and a 68% increase in VMN and DMN 125leptin receptor binding, respectively, compared to Sed rats. These data suggest that post-weaning exercise permanently lowers body weight by increasing central leptin sensitivity in DIO rats that are inherently leptin resistant.
ALTERED EXPRESSION OF APPETITE-ASSOCIATED RECEPTORS IN NODOSE GANGLION BY HIGH FAT DIET. ; 1UC Davis School of Veterinary Medicine, 22USDA/Western Human Nutrition Research Center
Food intake is modulated by both humoral and neuronal pathways; there is evidence that maintenance on a high fat diet leads to hyperphagia, in part via a peripheral, CCK-dependent vagal mechanism. We tested the hypothesis that a high-fat diet induces hyperphagia by altering expression of genes involved in the short-term regulation of food intake in vagal neurons. Methods: Sprague-Dawley rats were maintained on low fat (10%) or high fat (45%) diet. After 1 or 8 weeks on the diets, blood samples were collected from fasted rats to determine plasma levels of leptin and insulin. Nodose ganglia from individual rats were collected and real-time RT-PCR for receptors performed. Results: Rats fed a HF diet and prone to obesity (DIO-P) presented hyperleptinemia, hyperinsulinemia compared to LF or HF diet-induced resistant rats (DIO-R). The expression profile of receptors involved in appetite regulation (CB1, FAAH, GHSR and CCK1R) was increased over 2-fold in nodose ganglia of DIO-P rats, but not in LF fed or DIO-R rats. No change was observed for the leptin receptor or PYY2R. Conclusion: The expression profile of receptors in the nodose ganglia is modified by diet. This suggests neurochemical reprogramming of vagal afferents which may contribute to altered food intake and obesity.
I CRAVE IT BUT I DON&RSQUO;T LIKE IT. ; Monell Chemical Senses Center
Liking and craving are salient features of our reactions to foods. Drug addicts sometimes crave drugs that they no longer like. In contrast, food craving is usually associated with strong liking. There is also a great deal of evidence that drug craving is learned. Yet, we do not understand how food cravings come to be. So the goals of this study were to determine whether we could train subjects to crave a food that they had never craved before, and whether we could train subjects to crave a food that they did not like very much. Participants (N=23) consumed a vanilla-flavored dietary supplement beverage every day for 14 days. Half of the subjects consumed the beverage when fed and the other half consumed it when hungry. During the 14 days of training, we had spontaneous reports of craving for this beverage accompanied by neutral or dislike ratings from about 1/3 of the subjects. There was no effect of the hungry/fed condition. There also did not appear to be a learning curve; the cravings began to appear on the second day of the study and did not increase in frequency. Therefore an attentional mechanism rather than a Pavlovian process may be at work here. This is, to our knowledge, the first experimental demonstration of a craving-liking distinction for food. This result may have clinical relevance for bringing about diet change.
NEED-INDUCED SODIUM APPETITE IN SHR IS ENHANCED AFTER ONE EPISODE OF WATER DEPRIVATION-PARTIAL REPLETION (WD-PR) AND ENHANCEMENT IN SODIUM APPETITE IS DELAYED AFTER MULTIPLES EPISODES.. ; UNESP
SHR have an increased need-free ingestion of sodium solutions due to high cRAS activity, which mediates WD-PR induced Na+ appetite in HTZ rats. The objectives were to investigate Na+ appetite in SHR submitted to one WD-PR and Na+ appetite enhancement in SHR treated repeatedly. Adult male SHR, WKY and HTZ (n=6-12) were either not deprived, one or multiple WD-PR, and all underwent respective SAT. After 26h WD-PR, SHR ingested (ml) more 1.8% NaCl (4.5±0.2) than WKY (0.7±0.2) and HTZ (1.2±0.5). Right before access to 1.8% NaCl, Fos-ir (positive nuclei/10-3 mm2) was enhanced in SHR compared to both WKY and HTZ in the SFO (11.0±3.0, 6.5±1.1, 5.0±1.3, respectively), pre-LC (4.8±1.4, 1.7±0.4, 1.9±0.6) and comNTS (3.0±0.7, 0.9±0.3, 1.2±0.4). During multiple WD-PR, the 1.8% NaCl intake (ml) enhanced in all subsequent SAT when compared to the 1st in WKY (1.4±0.2, 1.2±0.1, 1.6±0.3, 2nd to 4th respectively) and in HTZ (3.6±0.6, 3.1±0.4, 2.2±0.7). Only the last SAT showed enhancement in SHR (4.5±0.2, 4.2±0.2, 5.5±0.2). SHR showed higher Na+ intake than normotensive strains in both SAT and the non-deprived state. The increased Fos-ir in the SFO, pre-LC, and comNTS suggest that these areas may trigger and/or drive the enhanced Na+ appetite exhibited by SHR. Moreover, the SHR´s delayed enhancement of Na+ appetite facing repeated episodes of WD-PR could be due to their high cRAS activity.
HYPOTHALAMIC GENE EXPRESSION AND ANGIOTENSIN RECEPTOR (AGTR) TYPE-1 PROTEIN FROM DIFFERENT BRAIN AREAS IN HYDRATED ANIMALS SUBMITTED TO A SINGLE OR MULTIPLE WATER DEPRIVATION-PARTIAL REPLETION (WD-PR).. ; 1UFSCar/UNESP, 2InCor-USP, 3UTHSCSA, 4UNESP, 5InCor-IPq-FMUSP, 6ICB-USP
Repeated episodes of WD-PR enhance need-free and induced Na+ intake. The cRAS mediates WD-PR induced Na+ appetite, but the central mechanisms involved in the enhancement of need-free Na+ intake are not well established. We investigate hypothalamic gene expression and cAgtr1 protein in hydrated animals submitted to one or repeated WD-PR. Adult male age-matched SD rats (3-9) were either not deprived or subjected to 1 or 3 WD-PR, and sacrificed in a hydrated status. In one set, the whole hypothalamus was removed for microarray study validated by qRT-PCR. The analysis included Crh, Agtr1a, Syt9 and Oxtr. In a second set, total protein from the OVLT, SFO, PVN, SON, and AMY´s brain punches was subjected to Western-Blot for Agtr1 expression. Densitometric measurements of the ir bands for Agtr1 were normalized using β-actin. Hypothalamic gene expression of Agtr1a was increased by 76% after a single WD-PR compared to control group. Gene expression of hypothalamic Crh, Syt9, and Oxtr were not altered within groups. Agtr1 protein expression was decreased by 45% in the SFO after both 1 and 3 WD-PR, but no changes were observed in OVLT, PVN, SON, and AMY. In conclusion, the neural substrate for the enhancement in the need-free sodium intake might not be the same as in the substrate for induced sodium appetite.
OXYTOCIN ENHANCES GLUTAMATERGIC AFFERENT TRANSMISSION AND PRODUCES AN INWARD CURRENT IN SECOND ORDER MEDIAL SOLITARY TRACT NEURONS. . ; Oregon Health and Science University
Vagal afferents contact neurons within the NTS
and evoke homeostatic reflex pathways. Descending projections from the PVN
release oxytocin to modulate afferent communication with NTS neurons, however,
the mechanisms through which oxytocin acts are poorly understood. From male
Sprague-Dawley rats, horizontal brainstem slices containing the solitary tract
(ST) and medial NTS were isolated under deep isoflurane anesthesia. Brain
slices were maintained in physiological bath and whole-cell patch clamp
recordings were made under voltage clamp. Remote electrical shocks to the ST
produced highly consistent glutamatergic EPSCs and identified NTS neurons
receiving direct ST afferent innervation. Oxytocin increased the amplitude of
ST-evoked EPSCs with no effect on event kinetics. Variance-mean analysis of
ST-evoked EPSCs indicates oxytocin increases the release probability of glutamate
from the afferent terminals suggestive of a presynaptic site of action. Glutamate
mediated miniature EPSCs (mEPSCs) were isolated with TTX and gabazine. Oxytocin
increased the frequency of mEPSCs but had no effect on the event kinetics. The
oxytocin receptor antagonist blocked this effect on mEPSCs. In addition,
oxytocin (1000 nM) evoked an inward holding current; consistent with postsynaptic
modulation of ion channels. Taken together these findings suggest oxytocin
released from PVN projections may enhance glutamatergic vagal afferent
transmission within NTS via both pre- and postsynaptic sites of action.
HL-088894 (JHP) and HL-041119 (MCA)
THE CENTRAL SIGNALING PATHWAYS OF AMYLIN: A NEUROANATOMICAL STUDY. ; Institute of Veterinary Physiology, Zurich Center for Integrative Human Physiology, Zurich University
Peripheral amylin inhibits food intake via activation of the area postrema (AP). This
activation is synaptically transmitted to the nucleus of the solitary tract (NTS), lateral parabrachial nucleus (LPB), central amygdaloid nucleus (Ce) and bed nucleus of stria terminalis (BST). Interestingly, neurons of the lateral hypothalamic area (LHA), which are activated during fasting, are indirectly inhibited by peripheral amylin.
Using a retrograde tracer (cholera toxin B, Ctb) we analyzed whether the LHA receives
neuronal projections from amylin-activated brain areas. The anterograde tracer biotinylated dextran amine (BDA) was used to confirm the projections. After Ctb injection into the LHA, 33% of amylin-activated (c-Fos positive) neurons in the LPB projected to the LHA. Only 9% and 7% of amylin-activated neurons from the NTS and BST, respectively, projected to the LHA, while no projections from the AP and Ce were found. Anterograde tracing produced consistent results. Besides ascending projections within the AP-BST axis, we also identified dense projections from the LPB to the ventromedial and paraventricular nuclei.
The LPB appears to be the main relay for amylin signal from the AP/NTS region to the LHA, mediating the amylin-induced inhibition of LHA. In addition to conveying excitatory input from the AP/NTS to the Ce and BST, the amylin-activated LPB area also projects to other hypothalamic feeding centers that may be involved in amylin’s anorectic action. Detailed knowledge of amylin’s mode of action is important for its clinical use in obesity treatment.
INTAKE OF A HIGH PROTEIN REGULAR SNACK IS CALORIC COMPENSATED IN HUMANS . ; 1INRA, AgroParisTech, UMR914 Nutrition Physiology and Ingestive Behavior, CRNHIdF, 2Department of Gastroenterology, Avicenne Hospital, AP-HP, CRNH-IdF
Snacking is often regarded as one of the causes of overweight. However, the main question is to determine if the consumption of snacks leads to an increase of energy intake or if at the opposite, there is a phenomenon of compensation maintaining constant daily energy intake. Answers to this question depend on numerous factors like the amount of energy or macronutrients in the snack and the concept of conditioning to the snack (learned satiety).
The objective of this study is to determine if the repeated consumption of a high-protein
snack given as preload alters energy intake at the next meal and throughout the day and if this kind of snack is compensated. In experiment 1, we measured the effect of two HP snacks after a training period (5 days) of consumption. We used a moderate amount of proteins (23g) and two types of milk proteins were compared. In experiment 2, we determined the importance of conditioning by comparing effect of the consumption of a HP snack on energy intake the first time subjects ingested the snack and after 5 days of repeated consumption of the same snack (training period).
The main result of our work is that for both proteins used, a HP snack given one hour before a meal, leads to partial energy compensation at the following meal and to over-compensation concerning the whole day energy consumption. We did not show a conditioning effect on food intake likely because our snack (cheese portion) was too familiar to volunteers.
OBESITY-PRONE RATS ARE LESS SENSITIVE TO THE SATIATING EFFECTS OF EXENDIN-4 THAN OBESITY-RESISTANT RATS. ; Pennington Biomedical Research Ctr
Several hormones produced in the gastrointestinal tract lead to decreased food consumption by producing signals which initiate feelings of fullness. Glucagon-like peptide 1 (GLP-1) is a satiety hormone made in the small intestine. Circulating GLP-1 levels are lower after a meal in obese people than lean controls, suggesting decreased feelings of fullness. Osborne-Mendel (OM) and S5B/Pl (S5B) rats were used to investigate the satiating effects of GLP-1. OM rats become obese when eating a high fat diet, whereas S5B rats do not become obese when eating the same diet. Experiment 1 examined the effects of Exendin-4 (Ex-4; GLP-1 agonist) administration on OM and S5B rats fed either a high fat (55%) or a low fat (10%) diet. It was hypothesized that S5B rats would be more sensitive to the satiating effects of Ex-4 than OM rats. The data indicated that Ex-4 dose-dependently decreased food intake to a greater extent in S5B rats, compared to OM rats. Intake of the high and low fat diets was differentially regulated by Ex-4 in these strains. Experiment 2 examined proglucagon mRNA expression in the distal intestine of OM and S5B rats. High dietary fat decreased proglucagon mRNA levels in the intestine of OM rats, but not in S5B rats. These data suggest that obesity-prone OM rats are less sensitive to the satiating effects of GLP-1 and produce less proglucagon mRNA when fed a high fat diet. Deficits in the response to and decreased expression of GLP-1 with a high fat diet, may be mechanisms through which OM rats overeat and gain weight. NIDDK32089 GAB
CONDITIONED ODOR PREFERENCES MEDIATED BY ASSOCIATIONS WITH LIKED TASTES. ; Arizona State University
Almond and banana extracts, which have strong odor components, were mixed with salt and saccharin in conditioned flavor preference learning. The results showed that mixing tastes with extracts increased liking for the extracts (measured by amount consumed in a test following training), but not the tastes. These findings are consistent with findings in humans suggesting that tastes can mediate increased liking to less preferred odors when they are mixed together. It is argued that since subjects typically express many more preferences for foods than aversions, it is particularly important to characterize this learning given its greater influence on diet and intake in the feeding context.
ADDICTION-LIKE BEHAVIORS IN RATS PREVIOUSLY MAINTAINED ON A HIGH-FAT DIET.. ; 1Dept. of Neural & Behavioral Sciences, Pennsylvania State University College of Medicine, 2Dept. of Nutrition, Pennsylvania State University
The present experiment investigated if addiction-like behaviors previously described by Deroche-Gamonet et al. (2004) are demonstrated in rats exposed to high-fat diets. Phase I. Access to fat. In accordance with the methodology of the Corwin lab (Dimitriou et al., 2000), non-food-deprived rats were maintained for 6 weeks on 1 of 4 diets: chow only (n=9); ad lib access to fat (n=21); 1 h daily access to fat (n=21); or 1 h access to fat on Monday, Wednesday, and Friday (n=21). Phase II. Cocaine self-administration. Rats were then returned to chow only diets, implanted with intrajugular catheters, and trained to self-administer cocaine (0.8 mg/kg) on a fixed ratio (FR) schedule of reinforcement, beginning at FR1 and increasing to FR5, and then FR20. Daily acquisition sessions consisted of 3 drug periods (40 min each), with successive drug periods separated by a non-drug period (15 min each). Results. Rats exposed to fat diets took more infusions than the chow group during FR5 trials and tended to display more goal-directed behavior during FR20 trials. Rats with a history of fat intake also displayed more goal-directed behavior during time out periods following each infusion and during signaled non-availability. These results suggest that a history of fat intake may predispose rats to exhibit more robust “addiction-like” behaviors toward a drug of abuse relative to rats maintained on a diet of standard laboratory chow. This work was supported by DA09815.
EFFECTS OF THE GABA AGONISTS, BACLOFEN AND MUSCIMOL, ON INSTRUMENTAL RESPONDING FOR FOOD REWARD . ; School of Life Sciences, University of Sussex
Intra-accumbens administration of the GABAA agonist muscimol or the GABAB agonist baclofen strongly stimulates eating behaviour in the rat. However previous reports have suggested that neither agonist is likely to stimulate instrumental responding for food reward. In the present study, separate groups of Lister hooded rats (N= 12, 12) were trained on a modified second order schedule of responding, as a measure of appetitive responding for food, and then implanted with bilateral guide cannulae aimed at the nucleus accumbens shell. They were also habituated to the presentation of chow, as a measure of consummatory behaviour. They were tested on the second order schedule following administration of vehicle, baclofen (110, 220, 660 pmoles) or muscimol (220, 440, 660 pmoles). Subsequently, they were given a free feeding test following an identical sequence of drug administration. Baclofen stimulated intrumental responding at an intermediate dose (220 pmoles, p<0.01), whereas muscimol had no significant effect on responding at any dose. Baclofen and muscimol stimulated free food intake at both intermediate and higher doses. These data demonstrate that the effects of intra-accumbens administration of baclofen and muscimol on instrumental responding are not equivalent and also show a clear dissociation between the dose-related effects of baclofen on appetitive and consummatory components of feeding behaviour. Baclofen, perhaps through heterosynaptic modulation of other neurotransmitter systems within the accumbens, has broader effects on motivational processing than muscimol.
INSURANCE REQUIRED WEIGHT LOSS REGIMEN LED TO WEIGHT GAIN IN BARIATRIC PATIENTS PRIOR TO SURGERY. ; St. Luke's-Roosevelt Hospital, Columbia University
Most insurance companies require patients to complete a 6-mo medically-supervised weight loss regimen to be approved for bariatric surgery. Anecdotal evidence suggests that patients may not lose much weight; but this has not been documented in the literature. Data was collected from 22 (4M, 18F) recent (since 2005) bariatric surgery patients, BMI = 46.7± 7.5 SD, age = 36.3 ± 7.8 SD, who completed an insurance required weight loss regimen with their primary care physician (PCP). Data was also collected from 12 (2M, 10F) patients, BMI = 46.08 ± 4.5 SD, age = 39.75 ± 8.1, who more recently (2007) completed a structured 6-mo CBT group weight loss program specially designed for bariatric patients. During the 6-mo regimen prior to surgery, those in the PCP group actually gained weight, +2.3 kg ± 4.9 SD (t (21) = 2.2, p = 0.042). In contrast, those in the CBT program lost weight, -1.1 kg ± 5.0 (t  = -0.79, p = 0.44). A between group comparison showed marginal significance (F (1, 32) = 3.69, p = 0.06). All analyses were repeated controlling for sex and age with no significant change in results. Weight gain in the PCP group may be due to patients overindulging in their favorite foods knowing they would no longer be able to do so postsurgery. A structured CBT program may counteract this overindulgence effect, promoting weight loss instead of weight gain presurgery.
SCENT DEPENDENT LEARNING: THE EFFECTS OF AMBIENT CONGRUENT VS. INCONGRUENT SCENTS ON RECALL OF COFFEE INFORMATION. ; Wheeling Jesuit University
A connection between scent and memory has long been recognized. Scent dependent learning exists when the same scent is present in both the learning and assessment phase, which leads to greater performance. The present study assessed scent dependent learning interactions between scent congruent vs. incongruent information. Prior to participation, Ps completed the Profile of Mood States (POMS). They then watched a 50 min. video on coffee history under one of three ambient scent conditions (none, coffee, cherry). Following the video, a questionnaire related to the video information was completed under one of three ambient scent conditions (none, coffee, cherry). Following the questionnaire, Ps again completed the POMS, in addition to the NASA-TLX to determine perceived workload and task performance. Between-subjects ANOVAs were conducted controlling for coffee preference and consumption. Scent dependent learning was validated, such that performance was better when the same scent was in both the learning and recall situations. Recall was greater than control when the scent in both the learning and recall situations matched the information presented (i.e. coffee). Recall was greater than control when coffee scent was present in the recall situation, regardless of whether it was presented in the learning condition. Thus, scent dependent learning interacts with the type of information being presented, and can provide greatest performance with congruent testing information, even in the absence of that scent being presented in the learning condition.
EFFECTS OF PEPPERMINT SCENT ON APPETITE CONTROL AND CALORIC INTAKE . ; Wheeling Jesuit University
Previous research indicates that inhalation of certain scents may reduce hunger levels. The present study evaluated hunger levels during peppermint inhalation vs. non-inhalation, in addition to actual food consumption and dietary evaluation (e.g., fat intake, caloric intake, vitamin and mineral intake, etc.) over a period of two weeks. In a within-subjects design, participants completed a peppermint inhalation condition (administered every 2 hours) and a non-inhalation condition. Each condition was performed for 5 days during separate weeks. During the protocol, participant rated their hunger level every two hours and completed a food diary listing everything they consumed for the two five-day periods. Results indicate participants consumed significantly fewer total calories, calories from saturated fat, total fat, and sugar during the peppermint inhalation condition. Participants also rated their hunger level significantly lower during peppermint inhalation. The primary implication of these results is that peppermint scent can be used as an effective adjunct to decrease appetite, decrease hunger cravings, and consume fewer calories, which may lead to weight reduction and greater overall health.
INJECTIONS OF ESTROGENS IN YOUNG FEMALE RATS AND THEIR INTAKE OF PALATABLE INGESTA . ; Rensselaer Polytechnic Institute
Young female rats were used to assess the consequences of a single injection of estrone 3-sulfate (ES) or 17 alpha-ethynylestradiol (EE), 0.38 mg/kg, or their carrier (placebo) on daily intake of palatable ingesta, chocolate cake mix batter (CCMB). Previously, it was shown that estradiol valerate increased intakes of CCMB and a combination of both fat and sugar at 0.38 mg/kg, as well as other doses, for a number of days post injection provided that intakes were not measured just after injections. The initial effects of EV (and other estrogens) are significant reductions in bodyweights and intakes establishing a conditional state that biases further intakes. When the initial effects (as indexed by bodyweight-loss) are separated from subsequent intakes, EV enhances intakes of palatable ingesta. The effects (g of CCMB eaten and bodyweights) of ES and EE were assessed 4 days after injections for 10 days. EE, but not ES, produced reliable increments in intakes and bodyweights. Unlike conclusions appearing in the literature, estrogens can produced marked increments in intake of ingesta among laboratory animals, provided the presented ingesta are highly palatable and not associated with initial weight loss that typically results from injections. Given these findings, there should be a further consideration of the idea that estrogens, when given as medicines to women, are salient with respect to obesity.
COMPETITION AMONG WOMEN INFLUENCES SUBSEQUENT FOOD CHOICE. ; University of Toronto Mississauga
Previous evidence suggests that if performance is threatened in one domain people will perform significantly better in a different domain in order to repair self-regard. In the present study we are interested in eating as a domain in which women might engage in such image-restoring behavior. We examined women’s food choices after exposure to a threatening upward social comparison in an achievement situation. On the pretext of a two-study session, participants volunteered for a study examining the effect of hunger on performance of a series of competitive skill-related tasks and for a consumer taste test. Some participants were led to believe that their competitor (a confederate) performed much better than they did (high threat), while others performed the tasks under non-competitive conditions (low threat). They were then given a choice of which of seven versions of lasagna they would eat and rate in the consumer taste test; these seven versions differed in terms of their caloric content/healthfulness. It was expected and found that participants in the high threat condition, in comparison to those in the low threat condition, would be highly motivated to restore their sense of self-worth by successfully competing in an area unrelated to the original inferiority and would, therefore, choose a lower calorie/more healthful version of the lasagna. The results are discussed in terms of the centrality of a slender body as a feature of the contemporary ideal of female attractiveness. It is argued that, because it is so difficult to achieve, a thin body is a status symbol for women and striving for it is a form of achievement behavior.
ONDANSETRON BLOCKS LICL CONDITIONED PLACE AVOIDANCE (CPA) BUT NOT CONDITIONED TASTE AVOIDANCE (CTA). ; Dept. of Neuroscience, University of Pittsburgh
CTA typically is interpreted as sufficient evidence that a drug or treatment is aversive to rats. For example, LiCl induces oral gaping and other signs of nausea in rats and mice, and LiCl supports robust CTA. However, Linda Parker and colleagues have demonstrated that many agents that support CTA also support appetitive behavior and conditioned place preference (e.g., morphine, cocaine), suggesting that CTA is insufficient to reveal negative hedonic state. They report that the anti-nauseogenic 5-HT3 receptor antagonist ondansetron (OND) blocks unconditioned and conditioned gaping responses to LiCl in rats, without attenuating CTA. We examined whether OND also blocks LiCl-induced CPA. On two separate conditioning days, adult male Sprague-Dawley rats were injected i.p. with a 1% BW volume of 0.15M LiCl containing 1.5% saccharin (sac) on one conditioning day, and with saline on another. Other rats were injected with saline + sac one day, and LiCl alone on another day. Rats were placed into a confined chamber of a 3-chamber CPA box for 30 min after i.p. injection. On testing days, all rats displayed significant CPA of the LiCl-paired chamber. Rats that received LiCl + sacc also displayed significant CTA of sacc in a subsequent bottle test. Thus, LiCl simultaneously conditioned both place and taste avoidance. In the second experiment, OND before LiCl eliminated CPA but did not reduce CTA to sacc. These results indicate that CPA testing is better than CTA testing as an indicator of nausea, malaise, aversion, and other negative affective states.
ESTRADIOL&RSQUO;S INFLUENCE ON TRYPTOPHAN-HYDROXYLASE 2 GENE EXPRESSION IN RAPHE NUCLEI.. ; Program in Neuroscience
Emerging evidence suggests that the anorexigenic effect of estradiol benzoate (EB) is mediated, in part, via its ability to increase serotonin (5HT) signaling at the genomic level in the dorsal and medial raphe nuclei (RN). We recently found that EB-treated, ovariectomized (OVX) rats show increased expression of Pet1, a transcription factor that promotes the expression of many 5HTergic genes. Here, we hypothesized that EB increases the expression of tryptophan hydroxylase (TPH2), the gene encoding the rate-limiting synthetic enzyme for 5HT in the RN, which also contains an upstream Pet1-binding site. OVX rats received 0, 2, or 10 µg EB in sesame oil sc on 2 consecutive days. Two days later, EB-treated rats displayed decreases in food intake and body weight relative to controls. The rats were perfused, brains were removed, and coronal sections were cut through the RN. TPH2 gene expression was assessed by in situ hybridization on free-floating sections using a 35S-labeled cDNA probe. Our preliminary data (n=4/group) showed no change in TPH2 mRNA in the RN of EB-treated rats, relative to controls (pixel density: 2 µg (24.8±3.1) and 10 µg (23.8±1.9) vs. 0 µg (22.8±2.5), n.s.). This suggests that the anorexigenic effect of estradiol is not mediated via an increase in the transcription of the major synthetic enzyme for 5HT. Further studies are required to determine whether an increase in TPH2 protein levels or in levels of releasable 5HT contribute to the increased serotonergic tone and anorexia in estradiol-treated, OVX rats. Supported by DK073936 and DC00044.
UNDERSTANDING SENSORY-SPECIFIC SATIETY IN A SNACK CONTEXT . ; 1University of Sussex, 2Mars
Sensory-specific satiety (SSS) in humans is defined as a decrease in liking or a consumed food relative to other non-consumed items. Accordingly, decline of liking should be the same for a food eaten on its own or in the context of pre-consumption evaluations of other foods. However, some studies suggest that the size of the SSS effect is greater if the consumed item is eaten after evaluations of several foods than on its own, implying an element of contrast effect in SSS. Accordingly, three experiments tested whether manipulating the number and type (sweet vs savoury) of uneaten foods assessed before consumption affected the extent to which SSS developed in a snack context. Female participants attended a single SSS test session with either a sweet (experiment one, n=56), savoury (experiment two, n=30), or both sweet and savoury snacks (experiment 3, n=64). Experiment one suggested that the magnitude of SSS increased linearly with rising numbers of uneaten foods. In contrast, Experiment two found no significant differences in magnitude of SSS between conditions. Experiment three found no clear effects of number of pre-test conditions on SSS, with some evidence of greater generalization from uneaten to eaten savoury foods. These experiments suggest SSS is a robust effect which is largely unaffected by contrast effects between eaten and uneaten foods, but SSS may be less reliably demonstrated where uneaten foods are too few or too similar to the eaten item.
IRONIC EFFECTS OF SUPPRESSING FOOD THOUGHTS?. ; Maastricht University
Restrained eaters chronically attempt to refrain from eating high-fat palatable foods, but they often fail. According to Wegner (1994), people can exert self-control when there is no cognitive load, but they fail when a high cognitive load is present. In two experiments, the hypothesis was tested that people can suppress thoughts of high-fat palatable foods when there is no cognitive load, but suffer from a surge of exactly those thoughts they want to avoid when they do experience a high load. Participants were either instructed to concentrate on or to suppress thoughts of high-fat palatable foods, both before and during performance of an emotional Stroop task, which measured the accessibility of high-fat food-words. Accessibility of food-words was indexed by a food-words – neutral-words difference score of color naming latencies. In both experiments, for low cognitive load, food words were more accessible in the concentrate condition than in the suppress condition, whereas for high load, the concentrate and suppress condition did not differ. For high as compared to low load, the accessibility of food words tended to increase in the suppress condition in both experiments, whereas a tendency towards decreased accessibility (Exp 1) or a similar level of accessibility (Exp 2) was found in the concentrate condition. Thus, a high cognitive load makes the suppression of thoughts about high-fat foods difficult; however, it does not result in Wegner’s ironic effect, as thoughts about high-fat foods are not more accessible during suppression than during concentration when participants experience a high cognitive load.
THE RELATIONSHIP BETWEEN DIETARY ENERGY DENSITY AND ENERGY INTAKE . ; Department of Nutritional Sciences, The Pennsylvania State University
Large portions of energy-dense (kcal/g) foods are associated with excess energy intake. The main dietary components that affect energy density (ED) are the water content, which decreases ED, and the fat content, which increases ED. Foods low in ED can enhance satiety by providing consumers with satisfying portions, even when calories are restricted. Lab-based studies indicate that people tend to eat a consistent amount of food, so that reductions in the ED of the diet are associated with a reduction in energy intake without an increase in hunger. Three clinical trials have shown that reductions in the ED of the diet by the addition of water-rich foods such as fruits and vegetables are associated with substantial weight loss even when patients are not told to restrict calories. Population-based studies also show that dietary ED is related to energy intake, the amount of food consumed, diet quality, and weight status. Recent studies in 3- to 5-year old children show that, as in adults, children tend to eat a consistent weight of food when the ED of the available foods is reduced. Therefore, lowering the ED decreases children's energy intake and this effect persists for up to 2 days. Lowering the ED of the diet could provide an effective strategy for the prevention and treatment of obesity, while improving diet quality.
SYNAPSES AND SIGNALS IN THE PERIPHERAL SENSORY ORGANS OF TASTE . ; 1Dept of Physiology & Biophysics, Miller Sch Med, U Miami, 2Program in Neurosciences, U Miami
Previous views of taste buds include that these peripheral sensory structures are merely passive interfaces between the external chemical environment of the oral cavity and sensory afferent neurons leading into the brain. The role of taste buds was viewed as simply converting sapid stimuli into electrical impulses in primary afferent fibers. Sensory neurobiologists now understand that taste buds are not passive interfaces and that a considerable degree of signal processing occurs in taste buds. Synaptic interactions between taste bud cells helps shape the output of these peripheral sensory organs. Recent studies have identified some of the key neurotransmitters involved in taste bud signal processing and have revealed novel transmitter release mechanisms.
I will present some of these new findings about peripheral signal processing and discuss how taste buds respond to and encode sweet, sour, salty, bitter, and umami tastes.
Supported by NIH/NIDCD grants 2R01DC00374 and 5R01DC007630 to SR.
ACUTE STRESS-RELATED CHANGES IN EATING THE IN ABSENCE OF HUNGER . ; Humane biologie, Maastricht University
Background: obesity results from a chronic deregulation of
energy balance, which may be caused by stress.
Objective: to investigate the effect of acute and psychological stress on eating in the absence of hunger, in normal- and overweight men and women. Moreover, possible subject specific features, like eating behavior were taken into account.
Methods: in 129 subjects (BMI 24.5±3.4 kg/m2; age 27.6±8.8y) we determined Three Factor Eating Questionnaire scores (F1 = 7.2±4.4; F2 = 4.5±2.6; F3 = 3.9±2.6) and STAI trait scores (31.7±24.2), and performed in a cross-over design an ‘eating
in absence of hunger’ protocol in combination with a stress or control task and
STAI state score measurements.
Results: energy intake from sweet foods (708.1 vs. 599.4 kJ,
p<0.03) and total energy intake (965.2 vs. 793.8 kJ, p<0.01) was
significantly higher in the stress compared to the control condition.
Differences in energy intake between the stress and control condition were a
function of differences in STAI state scores between immediately after compared
to before the stress task (∆ STAI state score) (R2 = 0.05, p<0.01). This positive relationship was stronger in subjects with a high disinhibition score (R2 = 0.12, p<0.05). Linear regression showed a relationship of ∆ STAI state score with body weight, and STAI trait score (R2= 0.209, p<0.05). Conclusion: acute stress leads to eating in absence
of hunger, especially in vulnerable individuals characterized by overweight and
sensitivity to chronic stress.
SOMATOSTATIN AND CORTICOTROPHIN RELEASING FACTOR LOCALIZATION IN FOREBRAIN NEURONS PROJECTING TO THE PARABRACHIAL NUCLEUS.. ; University of Louisville School of Medicine, Department of Anatomical Sciences and Neurobiology
The lateral hypothalamus (LH), central nucleus of amygdala (CeA), bed nucleus of the stria terminalis (BNST), and gustatory insular cortex (GC) receive taste information from the pontine parabrachial nucleus (PBN). These forebrain areas, in turn, send projections back to the PBN that modulate gustatory elicited neural responses. This study investigated the localization of somatostatin (SS) and corticotrophin releasing factor (CRF) in ventral forebrain neurons that project to the gustatory responsive PBN. The taste responsive region was localized electrophysiologically and the retrograde tracer Fluorogold (FG) was iontophoretically ejected (+2µA, 2 minutes on/1 minute off for 25 minutes). Seven days later, the animals are euthanized and tissue sections containing the LH, CeA, BNST, and GC were processed for co-localization of FG with SS and CRF. In each forebrain site, immunohistochemical processing for SS and CRF resulted in robust labeling of cells with distinguishable nuclei and short processes. The incidence of FG/SS co-localization was greatest in the CeA compared to the other forebrain sites examined. For CRF, the percentage of double-labeled neurons was more equally distributed across forebrain sites. The present results suggest that the influence of descending forebrain inputs on parabrachial taste processing could be mediated, in part, by the release of somatostatin and/or CRF.
SOCIAL INFLUENCES ON CHILDREN AND YOUTH FOOD INTAKE . ; SUNY Buffalo
Present a series of studies on the effects of social influence on eating and activities in overweight and non-overweight youth. This research exemplifies how social isolation resulting from teasing and weight criticism may decrease the motivation to be physically active and involved with peers and increase the reinforcing value of eating and sedentary solitary activities. The author will present an integrative model which accounts for the role of peer relationships, or the lack thereof, on youth's eating and physical activity. Implications for researchers and clinicians will be discussed.
FEMALE RATS ARE RELATIVELY MORE SENSITIVE TO REDUCED LIPID- THAN TO REDUCED CARBOHYDRATE-AVAILABILITY. ; University of Cincinnati
Females (humans and rodents) have blunted counter-regulatory responses to hypoglycemia relative to males, suggesting that females have reduced sensitivity to changes in carbohydrate availability. This led us to hypothesize that females would have greater sensitivity to changes in lipid availability. To assess this, we performed dose response studies to examine the feeding response to glucoprivation (IP 2-deoxyglucose; 2DG) and lipoprivation (IP mercaptoacetate; MA) in age-matched male and female Long-Evans rats. Males significantly increased food intake after 250 and 750 mg/kg of 2DG (2.8 ± 0.4 and 2.9 ± 0.5 vs. 1.3 ± 0.3 g for 250 and 750 mg/kg 2DG vs. saline, respectively) whereas females increased feeding only after 750 mg/kg of 2DG (3.3 ± 0.3 vs. 1.8 ± 0.3g in 2DG vs. saline, respectively). The glucose (AUC 16,575 ± 1667 vs. 4665 ± 2039 mg/dl*min; p<0.01) and glycerol (AUC 168 ± 28 vs. 89 ± 22 mg/dl*min in males vs. females, respectively) responses to 250 mg/kg of 2DG were significantly greater in males vs. females. With the same absolute dose of 2DG (130 mg), the glucose and glycerol AUCs were ~37% and 27% lower in females vs. males. In contrast, females had a significant increase in food intake 3 h after all doses of MA (2.4 ± 0.3, 2.2 ± 0.4 and 2.7 ± 0.3 vs. 1.6 ± 0.2g in 115, 200, and 355 mg/kg MA vs. saline; p<0.05), whereas males increased food intake only with the highest dose of MA (1.9 ± 0.4 vs. 0.9 ± 0.4g in 355 mg/kg MA vs. saline, respectively; p>0.05). Neither males nor females had a significant increase in glucose or glycerol in response to 200 mg/kg of MA. These data suggest that male and female rats have differential sensitivity to nutrients, with males relatively more sensitive to deprivation of glucose and females relatively more sensitive to deprivation of fat. Further research will examine the CNS mechanisms for these differences.
NIH NIDDK K01DK075365-01
DIET-INDUCED OBESITY IN THE RAT IS INFLUENCED BY SEX AND EXERCISE. ; Florida State University
Previously, our group demonstrated that female rats are more vulnerable than male rats to diet-induced hyperphagia. Here, we examined whether this sex difference would persist during extended exposure to a highly palatable diet. Male and female rats (n=63) were housed in custom-designed cages that provided access to either a standard chow diet (CD) or a more palatable diet (PD) consisting of chow plus sweet milk. Half of the rats in each diet condition were given the opportunity to exercise in running wheels (RWs). Body weight (BW), food intake, vaginal cytology and RW activity were measured daily for 34 days. At the end of the experiment, animals were decapitated and visceral fat pads were measured and blood was collected. In both sexes, access to the PD produced a 30-35% increase in daily caloric intake. Despite similar hyperphagia, a sex difference in body weight gain was detected (males: 10% increase, females: 20% increase). Moreover, the deposition of body adiposity was directly influenced by exercise. In PD-fed males, exercise lessened the accrual of body fat (increase in body fat: 29.7 ± 3.7 g (sedentary) vs. 20.7 ± 3.2 g (active), p <0.05). A similar relationship was not observed in females (increase in body fat: 37.8 ± 3.2 g (sedentary) vs. 34.2 ± 3.1 g (active), n.s.). Taken together, our data suggest that females are more vulnerable than males to this form of diet-induced obesity. Our data further suggest that this effect is not mediated by sex differences in caloric intake. Rather, it appears to be mediated by sex differences in energy expenditure. Supported by DK73936.
PPAR&GAMMA; IS EXPRESSED IN HYPOTHALAMIC NEURONS INVOLVED IN FOOD INTAKE AND ENERGY HOMEOSTASIS.. ; 1University of Washington, 2Vanderbilt University
PPARγ is a ligand-activated transcription factor that exists in two isoforms, PPARγ1 and PPARγ2, with the latter thought to be restricted to adipocytes. In addition to increasing insulin sensitivity and adipogenesis, PPARγ agonists cause weight gain and hyperphagia. Given the central role of the hypothalamus in the integration of signals controlling energy homeostasis, we hypothesized that PPARγ is expressed in this brain region. In rat hypothalamus, immunoreactive PPARγ staining was concentrated in the arcuate nucleus (ARC) and ventromedial nucleus (VMN), two key areas strongly implicated in the control of energy homeostasis. Staining with a PPARγ2-specific antibody revealed the same distribution. Within the ARC, PPARγ was identified in two key neuronal subsets involved in energy homeostasis - those expressing proopiomelanocortin (POMC) and those expressing neuropeptide Y/agouti related protein (NPY/AgRP). Moreover, PPARγ mRNA levels are dramatically reduced in the hypothalamus of mice with neuron-specific deletion of PPARγ, confirming that neurons are the primary source of PPARγ. That hypothalamic PPARγ is transcriptionally active is suggested by increased hypothalamic expression of the PPARγ target gene, lipoprotein lipase, in response to rosiglitazone administration at a dose (6mg/kg/d) sufficient to increase food intake. Together, these data identify the hypothalamus as a potentially important target for the action of PPARγ.
PYY DECREASES FOOD INTAKE AND ACTIVATES PERIPHERAL AND CENTRAL NEURONS IN RATS.. ; College of Veterinary Medicine, Tuskegee University
PYY decreases food intake in several species, but its physiological status and mechanism(s) of action remain uncertain. To study this problem, we determined the effects of peripherally-administered PYY3-36 on food intake and on activation of enteric and hindbrain neurons. Experiment 1. Overnight food deprived adult male rats (n=17) received i.p. injections of PYY3-36 (15, 30, 60ug/kg) or saline immediately before presentation of 10% sucrose. Consumption of sucrose was recorded at 5-min intervals throughout a 120-min test period. No dose of PYY reduced initial food intake (0-45 min). All doses of PYY tended to reduce food intake at the 45-100 min period, but only 15ug/kg was consistently significant (p<0.05). All doses of PYY inhibited food intake more than vehicle during the final 20 min of the test period (p<0.01). Experiment 2. Adult male rats were injected with PYY3-36 30ug/kg i.p. or saline and sacrificed at 30, 60, 90 and 120 min post-injection (n=3 each). Fos-like immunoreactivity, a marker for neuronal activation, was quantified in the myenteric and submucosal plexuses of the duodenum and the dorsal vagal complex (DVC) of the hindbrain. PYY activated enteric neurons of the duodenum and all of the tested areas in the DVC. Activation of the enteric nerves peaked at 30 min whereas activation of the DVC was delayed until 90 min. Conclusions. (1) PYY reduces intake of 10% sucrose. (2) PYY activates enteric neurons and the DVC. (3) Activation of enteric neurons by PYY prior to activation of the DVC suggests that PYY acts peripherally before acting centrally. Supported by P20MD000195-05 from the National Center on Minority Health and Health Disparities (Luther Williams, PI), NIH S06/GM08091, the Birmingham Racing Commission, The 2007 United Negro College Fund for the Henry C. McBay Research Fellowship.
EXENATIDE REDUCES FOOD INTAKE AND ACTIVATES THE ENTERIC NERVOUS SYSTEM OF THE GASTROINTESTINAL TRACT AND THE DORSAL VAGAL COMPLEX OF THE HINDBRAIN. ; Tuskegee University
Exenatide is a synthetic agonist of the glucagon-like peptide-1 (GLP-1) receptor, which is intended as an anti-diabetes drug. The goal of this work was to investigate the abilities of exenatide to reduce food intake and activate the enteric neurons of the gastrointestinal (GI) tract of the duodenum and the dorsal vagal complex (DVC) of the hindbrain. Experiment 1: Five groups of 15-h food deprived Sprague Dawley male rats were injected with Exenatide (0.1 [n=15], 0.5 [n=15], 5 [n=3] and 10 [n=3] ug/kg) or saline (n=21) intraperitoneally. Intake of 10% sucrose solution was measured at 5 min intervals for 120 min. Exenatide reduced sucrose intake dose dependently following the 20 min time point. Experiment 2: Following 15-h food deprivation, five groups of rats were injected with the treatments listed above and sacrificed 90 min following the injection. Enteric neurons (myenteric and submucosal plexuses) and DVC were processed for immunohistochemical detection of Fos, the protein product of the immediate early gene c-fos, used as a marker for neuronal activation. Exenatide increased Fos-like immunoreactivity dose-dependently in the myenteric and submucosal neurons of the duodenum and in DVC areas that regulate food intake e.g. area postrema, nucleus tractus solitarius and dorsal motor nucleus of the vagus. Conclusions: Exenatide reduces food intake, possibly by activating enteric and DVC neurons. Supported by Amylin Inc. grant.
CONDITIONED TASTE AVERSION (CTA) RETENTION (RT) AND EXTINCTION (EXT) AFTER GUSTATORY THALAMUS (VPMPC) LESIONS IN RATS.. ; Dip. Biomed. Sci., Physiology, University of Modena & Reggio E., Via Campi 287
The experiment was performed to ascertain if VPMpc is essential for RT and EXT of a presurgically acquired CTA. Subjects were 36 male rats. The experiment was divided in: Pre-surgical acquisition of CTA; VPMpc surgery and recovery; RT tests; EXT tests. Rats were matched for water intake (15 min) and split into two groups. Alanine 0.3 Mol was the conditioning stimulus (CS) and injections of 0.15 Mol LiCl was unconditional stimulus (UCS). After good baseline water intake, Alanine was offered to all rats (15 min). Then, one group (LiCl) received an ip injection of LiCl; the other (Saline) was injected with an equivalent volume of physiological saline. There were 3 such CS-UCS pairings. Rats of Saline and LiCl group where matched on the basis of alanine intake and divided in 3 sub-groups. Ten rats of Saline group (VPMpc-X-S) and 10 rats of LiCl group (VPMpc-X-LiCl), received bilateral injections of Ibotenic Acid (0.2 ml; 20 mg/ml) into VPMpc; 4 rats of Saline group (PBS-S) and 4 rats of LiCl group (PBS-LiCl) received bilateral injection of the same volume of vehicle; the last 4 rats of each group served as NSCnon surgical control. RT test consisted of two-bottle preference tests; rats had simultaneous access to water and alanine for 15min. CTA EXT was performed by one-bottle filled with alanine. Results showed that the integrity of VPMpc is not necessary for learning and expression of the CTA, and is not critical for RT and EXT of the presurgically acquired CTA.
FOOD VISCOSITY INFLUENCES CORE TEMPERATURE IN RATS. ; 1Department of Psychological Sciences, Purdue University, 2Department of Basic Medical Sciences, Purdue University, 3Ingestive Behavior Research Center, Purdue University
A hypothesized feature of energy regulation, caloric compensation is a decrease in caloric intake at one meal in response to excess intake at a previous meal; food viscosity may be one determinant of caloric compensation. The present study examined effects of food viscosity on core temperature as a function of amount of experience with a low viscosity food. Rats in Group Exposed were fed ad lib chow and given 10 daily exposures to 10 gm of low viscosity Ensure between each of four tests. Rats in Group Nonexposed were treated like Group Exposed, except no Ensure was given between tests. During each test, rats were 23hr food deprived and given a premeal of either low viscosity Ensure, or equicaloric high viscosity Ensure. Effects of each premeal type on core temperature, behavioral activity, and amount of chow consumed at a later test meal were measured. Premeal viscosity had little effect on core temperature increment or caloric compensation on Test 1. On Tests 2-4, the low viscosity premeal was followed by a smaller rise in core temperature and weaker caloric compensation in the Exposed group, compared to the Nonexposed group. A final test with two low viscosity premeals that differed in caloric and nutritive content indicated that the effects of viscosity on core temperature depend on learning viscosity cues predict the caloric consequences of food. The findings support a role for learning in energy regulation.
REGULATION OF FOOD INTAKE BY GONADOTROPIN RELEASING HORMONE II IN AN ANIMAL MODEL OF BINGE EATING DISORDER. ; Dept of Biochem and Mol Genetics University of Virginia
Binge eating disorder (BED) is characterized by recurrent short-term eating episodes, typically of high fat foods, in the absence of compensatory mechanisms (i.e. dieting, exercise, emesis). We have developed an animal model of BED using the musk shrew (Suncus murinus). Musk shrews of both sexes overeat when presented with a high fat food. Compensatory reduction of food intake is not seen in these animals. Gonadotropin releasing hormone II (GnRH II) is a structural variant of GnRH I that is widely expressed in mammals. GnRH II can affect food intake and likewise is affected by energetic status. Here we tested the hypothesis that GnRH II can inhibit high fat chow intake in the absence of food restriction. Preliminary results suggest that a single administration of 135-18, a specific GnRH II agonist (and GnRH I antagonist), will suppress intake of a high fat chow in the first hour after administration. Further research will determine if this peptide will suppress bingeing in those animals that display binge behavior. GnRH II is highly conserved, and could play a similar regulatory function in other mammals including humans. This work is supported by NIH grant R01 MH MH068729.
SEX DIFFERENCES IN COPING WITH "LEAN" AND "OBESE" POSTNATAL ENVIRONMENTS IN A RAT MODEL OF OBESITY. ; 1Bar-Ilan Univ, 2Johns Hopkins Univ
OLETF rats are heavier than LETO controls at birth and are hyperphagic from early in life. We cross-fostered to assess postnatal environmental influences on short and long term obesity. Body weight was measured from birth every fifth day and intake daily after weaning. An independent ingestion test was performed on postnatal day [PND] 10. At weaning and PND 90, plasma was collected for leptin and corticosterone , & fat pads were weighed. Estrous cycle was monitored from PND 40-75. Results: OLETF males and females raised by LETO dams were leaner than controls and showed normalized (to LETO controls) fat levels. LETO pups raised by OLETF dams were only slightly heavier than LETO controls, but with significantly higher % fat and leptin levels. In the independent ingestion test, the genotype of the pups, not the phenotype, determined intake: OLETF pups overate even when their body weight was normal. In contrast, LETO pups ate as controls regardless of their body weight or % fat. After weaning, even though they became overweight, OLETF males remained leaner than OLETF controls and ate less until adulthood. OLETF females recovered all the fat and weight. LETO males returned to their genotype, but LETO females ate more and presented higher % fat than controls until PND90. Estrous cycle structure was affected by postnatal environment in the direction of the opposite, fostering strain. Thus, a gender difference was found: Males were biased to a more "lean" adulthood, while females, though affected, showed almost complete recovery.
Support: NIH/NIDDK–RO1 DK57609
HEPATIC PORTAL VEIN DEAFFERENTATION HAS NO EFFECT ON THE SATIATING EFFECT OF A HP DIET. ; 1Nutrition Physiology and Ingestive Behavior, INRA / AgroParisTech, 2NOPA, UMR 1197, INRA
High protein diet-induced early satiety originates from either detection of dietary protein and amino acids during digestion or internal metabolic anorectic signals consecutive to protein ingestion. These signals are likely to be mostly conveyed by the vagus nerve. Whether vagally conveyed signals are necessary to elicit satiety remains highly controversial. Although previous work from our laboratory has shown that sub-diaphragmatic vagotomy is not sufficient to suppress high protein diet-induced decrease in food intake (L’Heureux-Bouron et al. 2003), it has been recently revealed that hepato-portal deafferentiation abolished the anorectic effect of proteins (Mithieux et al. 2005). This study aimed to clarify (i) the possible involvement of the vagus nerve in dietary protein detection and (ii) whether this information is necessary to elicit early satiety. Although electrophysiological recordings of 19 rats vagal nerve strands clearly established that intralumenal protein increased vagus nerve activity, capsaicin deafferentation of the hepato-portal vein did not abolish high protein diet-induced satiety. Together these data suggests that vagal afferents are involved in the detection of dietary protein but proposes also that neither hepato-portal nor sub-diaphragmatic vagal afferent conveyed information is necessary to elicit satiety.
ACTIVATION MAPS IN THE NUCLEUS OF THE SOLITARY TRACT (NTS) IN RESPONSE TO INTERNAL STIMULI. ; 1Nutrition Physiology and Ingestive Behavior, INRA / AgroParisTech, 2NOPA, UMR 1197, INRA
Integration of gut information by the NTS is involved in the induction of satiation during digestion. Little is known about the encoding of peripheral information by the NTS. Similarly to other sensory encoding processes, internal sensing may rely on stimulus specific activation patterns. We developed a technique that displays these activations patterns in the NTS in a three-dimensional model using intragastric loads of macronutrients as sensory stimuli. Male C57BL/6J mice were gavaged with isocaloric loads of either peptone or sucrose or trioleate. Animals were perfused and their brains collected and postfixed. Serial coronal brainstem sections (20 µm thick) covering the entire caudo-rostral extent of the NTS were collected. On odd- and even-numbered sections, respectively, immunodetection of Fos protein and luxol fast blue / neutral red staining were performed. Digitized brainstem images (20x) were acquired. Using Free-D, a 3D-reconstruction software, the contours of the brainstem and of the NTS were delineated and the Fos-positive neurons pointed. After registration, the piling-up of the segmentations yielded three-dimensional models of the NTS including the activated neurons. The density of Fos immunoreactive neurones in the brainstem of mice gavaged with different macronutrients will be compared.
EFFECTS OF INTRADUODENAL INFUSION OF VARYING COMBINATIONS OF LIPID AND CARBOHYDRATE ON ANTROPYLORODUODENAL MOTILITY, HORMONE RELEASE AND APPETITE IN HEALTHY MALES. . ; University of Adelaide Discipline of Medicine, Royal Adelaide Hospital
BACKGROUND/AIMS: Intraduodenal infusion of lipid and glucose suppress appetite and energy intake, modulate gastrointestinal motility, and stimulate cholecystokinin (CCK) secretion, with lipid being more potent than isocaloric glucose, and lipid, but not glucose, also stimulates peptide YY (PYY) secretion. We hypothesised that increasing the ratio of maltodextrin relative to lipid would reduce the effects on antropyloroduodenal (APD) pressures, stimulate less plasma CCK and PYY, and these changes would be associated with reduced suppression of appetite and energy intake. METHODS: 8 healthy lean males were studied on three separate occasions in double-blind, randomised order. APD motility, plasma CCK and PYY concentrations and appetite perceptions (desire-to-eat and prospective consumption) were measured during 90 min intraduodenal infusions of (i) 3 kcal/min lipid (“L3”), (ii) 2 kcal/min lipid and 1 kcal/min maltodextrin (“L2/CHO1”) or (iii) 1 kcal/min lipid and 2 kcal/min maltodextrin (“L1/CHO2”), and energy intake was quantified immediately afterwards at a buffet-style, cold lunch. RESULTS: Increasing the lipid content of the infusion was associated with greater suppression of antral and duodenal pressures and stimulation of PYY (r2>0.46, P<0.05 for all). There was a tendency for greater stimulation of plasma CCK during L3 compared with L2/CHO1 and L1/CHO2 (P=0.10). There were no differences in pyloric pressures between the three infusions. These effects were associated with greater suppression of desire-to-eat, prospective consumption and subsequent energy intake (r2>0.45, P<0.05 for all) with increasing lipid content of the infusion. CONCLUSION: Our data provide further evidence that specific modulations of gastrointestinal function by nutrients may be important contributors to the regulation of acute energy intake in healthy humans.
BRAIN APOLIPOPROTEIN E: AN IMPORTANT REGULATOR OF FOOD INTAKE AND BODY WEIGHT. ; 1Dept. of Pathology and Laboratory, 2Dept. of Psychiatry, Univ. of Cincinnati College of Medicine
The hypothalamus regulates ingestive behavior through multiple signaling systems. Here we report that apolipoprotein E (apoE) plays an important role in the regulation of food intake and body weight. Administration of apoE into the 3rd ventricle (i3vt) significantly decreased food intake and body weight in rats without causing malaise, whereas i3vt infusion of apoE antiserum stimulated feeding, implying that endogenous apoE tonically inhibits food intake. Consistent with this, apoE, as revealed by immunohistochemistry, was present in the hypothalamus, a brain site intimately involved in the integration of signals for energy homeostasis. Fasted rats exhibited significantly decreased apoE gene expression in the hypothalamus, and refeeding of these rats for 4 h evokes a significant increase of hypothalamic apoE mRNA levels. Both genetically obese (ob/ob) mice and high-fat diet-induced-obese rats had significantly reduced hypothalamic apoE mRNA levels, compared with their lean controls, suggesting that decreased apoE may contribute to hyperphagia in these obese animals. Additionally, our findings that apoE stimulated hypothalamic proopiomelanocortin gene expression in fasted rats and that SHU9119, a melanocortin 3/4 receptor antagonist, attenuated apoE’s inhibition of feeding, suggest that apoE’s anorectic action is associated with brain melanocortin signaling. Taken together, all of these findings demonstrate that brain apoE is an important regulator of food intake and body weight.
CENTRAL ANOREXIC ACTION OF BDNF IN MALE AND FEMALE RATS . ; University of Cincinnati
Experimental evidence implicates brain-derived neurotrophic factor (BDNF) in the regulation of energy balance. Mice with decreased expression of BDNF, or of its high-affinity receptor TrkB, are hyperphagic and obese; interestingly, this phenotype is more pronounced in females. BDNF and estrogen receptor α are highly expressed and partially co-localized in the ventromedial hypothalamus, raising the possibility that BDNF and estrogen interact to regulate energy balance. Therefore, we hypothesized that sex differences exist in the central anorexic action of BDNF, with females being more sensitive than males.
We first determined whether central administration of BDNF produces differential anorexic effects in male vs. cycling female rats. BDNF (0.1, 0.3, and 1.0 μg, i3vt) reduced food intake and body weight to the same degree in males and females. We then asked whether estradiol (E2) modulates hypothalamic BDNF expression by comparing BDNF mRNA levels in females across different phases of the estrous cycle as well as in ovariectomized (OVX) females vs. OVX females with E2 replacement. BDNF mRNA levels were similar across the estrous cycle and did not correlate with circulating E2 levels. However, OVX females in which E2 was replaced to supra-physiological levels had significantly more BDNF mRNA than OVX females. In conclusion, central administration of BDNF, at the doses tested, produced comparable anorexic effects in male and female rats. In addition, within the physiological range, E2 did not modify hypothalamic BDNF mRNA levels; however, when replaced at pharmacological doses, E2 significantly increased BDNF mRNA.
HYPOTHALAMIC AND HINDBRAIN PARENCHYMAL STUDIES SUPPORT A DISTRIBUTED VIEW OF MELANOCORTINERGIC CONTROL OF ENERGY EXPENDITURE AND FOOD INTAKE . ; UPenn
Human and animal data indicate that central melanocortin (MC) system is crucial role to energy balance (EB). Lateral icv delivery of MCR agonist (MTII) increases energy expenditure (EE) and decreases food intake (FI). As MCRs are anatomically distributed and lateral icv stimulation accesses many brain nuclei, it is unclear which receptor subpopulations mediate MCR effects. On the basis of selective MC4R re-expression, Balthasar et al.(2005) concludes that divergent MC4R populations control EE (hindbrain) and FI (hypothalamus). It is worth noting however, that MCR nuclei in both hypothalamus and hindbrain contribute to sympathetic outflow. We hypothesized that EE effects of MCR stimulation are obtained by selective stimulation of anatomically distinct CNS
nuclei. Here, an icv subthreshold dose of MTII (10pmol) was applied to sites within
hindbrain and hypothalamus; core temperature (Tc), heart rate (HR), spontaneous
activity (SPA) and FI were measured. MTII applied to raphe pallidus or NTS increased
Tc, HR, and SPA and decreased FI. RVLM or retrochiasmatic area MTII injection increased Tc, HR and decreased FI. PVN delivery increased HR and SPA, without changes in Tc. Anterior hypothalamic area injection was without effect. Results: 1) highlight MCR expressing nuclei previously unrecognized for their contribution to intake and EE control and 2) demonstrate that while MCR-mediated EB response profiles differ for each nucleus tested, MCR-elicited energetic and anorexic responses are not regionally divergent as they are elicited from multiple, widely distributed MCR populations.Supported by DK21397
JEJUNAL POUCH RECONSTRUCTION BUT NOT PRESERVATION OF DUODENAL PASSAGE AFTER TOTAL GASTRECTOMY REDUCES PLASMA CHOLECYSTOKININ AND PANCREATIC POLYPEPTIDE LONG TERM IN PIGS.. ; 1Lund University Hospital, 2Varberg County Hospital
Background The aim of the study was to evaluate the long-term effects of reconstructions of the gastrointestinal tract after gastrectomy, on fasting plasma levels of gastrointestinal hormones known to contribute to food intake controls and satiety. Methods Domestic Swedish pigs were randomly selected to sham surgery or gastrectomy followed by reconstruction; oesophago-jejunostomy on a Roux-en-Y loop (OJ-RY), jejunal interposition between the oesophagus and the duodenum (OJD), or an oesophago-jejunostomy with a jejunal pouch reservoir (J-pouch) on a Roux-en-Y loop. Blood was collected just before surgery and after three months. Plasma levels of peptides were analysed by RIA. Results Three months after surgery, levels of cholecystokinin and pancreatic polypeptide were significantly lowered (79.6% and 67.0 %, respectively) in animals with a jejunal pouch, but not in sham-operated animals or animals with OJ-RY or OD. There were no significant changes in fasting levels of NPY or PYY, irrespective of mode of reconstruction. Conclusion The present study shows that reconstruction with a jejunal pouch reservoir, but not preservation of duodenal passage, after total gastrectomy significantly lowered levels of CCK and PP, peptides considered to act in the periphery to reduce food intake.
THE ACUTE EFFECTS OF A LUNCH CONTAINING RESISTANT STARCH ON ENERGY AND SUBSTRATE UTILIZATION, GHRELIN, GLP-1, PYY CONCENTRATIONS, AND SATIETY. ; 1Maastricht University, Dept. of Human Biology, 2Top Institute Food and Nutrition, 3Technical University of Budapest, Dept of Biochemistry and Food Technology
Observations of epidemiological studies indicate that dietary fiber intake is involved in body weight control. A dietary fiber component that may be of specific importance is resistant starch (RS). Acute effects of RS on metabolism have hardly been studied and the effects of RS on ghrelin, PYY and GLP-1, in relation to changes in appetite are unknown. Thirty subjects (age: 31±14y, BMI: 23.8±2.8kg/m2) were studied 2 times in a crossover design. After 30 minutes resting on a bed, energy expenditure (EE) was measured and subsequently lunch was served (35% of daily energy requirement, 60%carbohydrates/10%protein/30% fat). The two lunch conditions were: i) normal pasta and ii) resistant starch pasta. During 3 h after the lunch diet induced EE was measured. Furthermore, visual analogue scales on the appetite profile were collected before and after lunch, and blood samples were taken for GLP-1, PYY, and ghrelin responses, before and after lunch. Satiety and EE were not different after RS lunch compared with the control lunch. Ghrelin, GLP-1 and PYY responses were not different between the RS lunch and the control lunch. In conclusion, RS supplementation has no acute effect on substrate utilization, appetite feelings, and gut derived hormones.
THE ACUTE EFFECTS OF A LUNCH CONTAINING CAPSAICIN ON ENERGY AND SUBSTRATE UTILIZATION, HORMONES, AND SATIETY . ; 1Maastricht University, Dept. of Human Biology, 2Top Institute Food and Nutrition
Addition of capsaicin to the diet has been shown to increase
satiety and thermogenesis. The effects of capsaicin on ghrelin, PYY and GLP-1,
in relation to changes in hunger and satiety are unknown. Thirty subjects (age:
31±14y, BMI: 23.8±2.8kg/m2) were studied 2 times in a randomized controlled
crossover design. After 30 minutes resting on a bed, resting metabolic rate was
measured by a ventilated hood system. Subsequently lunch (35% of daily energy
intake) was served. The two lunch conditions were: i) lunch without capsaicin
and ii) lunch with capsaicin (CAPS). The macronutrient composition (energy %)
of the lunches was: 60% carbohydrates/ 10% protein/ 30% fat. During 3 hours
after the lunch diet induced energy expenditure was measured. Furthermore
anchored 100mm visual analogue scales on the appetite profile were collected
and blood samples were taken for analysis of GLP-1, PYY, and ghrelin
concentrations, before and at different time-points after lunch. Satiety and
energy expenditure were not different after CAPS lunch compared with the
control lunch. Fifteen minutes after the lunch, CAPS lunch increased GLP-1
(p<0.05) and tended to decrease ghrelin (p=0.07) compared with the control
lunch. PYY responses were not different between the CAPS lunch and the control
lunch. Acute lunch containing capsaicin had no effect on satiety, EE, and PYY,
but increased GLP-1 and tended to decrease ghrelin.
ENERGY EXPENDITURE, PLASMA GHRELIN, GLP-1, PYY CONCENTRATIONS, AND SATIETY FOLLOWING A SINGLE HIGH PROTEIN LUNCH. ; Maastricht University, Dept. of Human Biology, TIFN
High-protein foods are more satiating and have a higher thermogenic effect than normal protein foods. We hypothesized that acute effects of higher protein intake on satiety may be related to acute metabolic and hormonal responses. Thirty subjects (age: 31±14y, BMI: 23.8±2.8kg/m2) were studied 2 times in a crossover design. After 30 minutes resting on a bed, energy expenditure (EE) was measured. Subsequently lunch (35% of daily energy requirements) was served. The two lunch conditions were: an appropriate protein (AP) lunch (10%protein/60%carbohydrate/30%fat), or a high-protein (HP) lunch (25%P/45%C/30%F). During 3 hours after the lunch diet induced EE was measured. Furthermore, visual analogue scales (VAS) on the appetite profile were collected and blood samples were taken for GLP-1, PYY, and ghrelin responses, before and after lunch.The increase in post-lunch EE tended to be greater after the HP (0.85±0.32kJ/min) than after the AP lunch (0.73±0.22kJ/min, p=0.07). The respiratory quotient did not differ between two treatments. VAS scores for satiety were significantly higher after the HP than after the AP lunch at 30 and 120min, and calculated as AUC (p<0.02). Effects of protein on satiety and diet induced EE did not happen simultaneously with plasma ghrelin, GLP-1 and PYY responses. A single HP lunch, therefore, does not exert its acute effect on satiety through increased concentrations of satiety related hormones.
FUNCTIONAL MRI OF THE HYPOTHALAMUS AS A BIOMARKER OF SATIETY? . ; 1Image Sciences Institute, University Medical Center Utrecht, 2TNO Quality of Life
Neuroimaging techniques allow the in vivo investigation of the central regulation of food intake. In the hypothalamus, multiple neural and hormonal signals relevant to food intake regulation are processed. Two earlier studies reported transient fMRI signal decreases in the hypothalamus after glucose ingestion. We aimed to evaluate the use of such fMRI measurements as a biomarker of metabolic satiety.
We observed a prolonged and, importantly, dose-dependent decrease in the hypothalamic fMRI signal within few minutes after the ingestion of glucose. This signal decrease proved to be specific to glucose insofar that no signal decreases were observed after ingestion of maltodextrin (energy / no sweet taste) and aspartame (no energy / sweet taste). Compared to ingestion of glucose, the hypothalamic response after intravenous (i.v.) glucose was smaller and less prolonged. In this experiment glucose administration was associated with decreased hunger and oral glucose tended to suppress hunger more than i.v. glucose. Moreover, the fMRI response correlated with hunger ratings after oral glucose. Another study showed that, in contrast with healthy controls, type 2 diabetics lack a decrease in the hypothalamic fMRI signal after oral glucose.
In summary, the hypothalamic fMRI response to glucose is a reproducible dose-dependent measure that is affected by preabsorptive signals and by pathology. So far, it has proven to be specific to glucose. Its dose-dependency and its correlation with hunger ratings after oral glucose make it an interesting candidate-biomarker of metabolic satiety.
OLFACTORY BULBECTOMY INCREASES THE INTAKE OF CORN OIL DURING SHAM FEEDING . ; Weill Medical College of Cornell University
Rats sham feed corn oil (Mindell et al., 1990). Thus, the orosensory stimuli of corn oil increase eating. Taste of fatty acids and texture of the oil have been proposed as important orosensory stimuli for increasing intake during sham feeding. Olfactory stimulation by the retronasal route could also be involved. To investigate that possibility, the 30-minute, sham-fed intakes of 4 concentrations of emulsified corn oil after 17 hours of food deprivation were measured in 11 intact rats (C) and 4 olfactory bulbectomized rats (OBX). Licking was measured and its rate and pattern were analyzed using the Quick Lick program. OBX rats sham fed 100% or more of all concentrations of corn oil than C rats (p <0.05). This increased intake was due to a significantly longer meal (p <0.05) in which the number of clusters increased significantly (p <0.05), but cluster size did not change. Thus, olfactory stimulation by corn oil in the mouth did not stimulate sham feeding; it apparently inhibited it. Supported by MH 00149.
RELATIONSHIPS BETWEEN ORAL SENSATION, FOOD HEDONICS, AND BODY MASS: ARE THE OBESE DIFFERENT? . ; 1Neuroscience, Yale University, 2Dentistry, University of Florida
To understand obesity, we need to consider why obese people consume more food than their bodies actually need. Do they experience food sensations differently; do they like them more? The easiest way to answer these questions is to ask obese and nonobese individuals to rate the intensity of their sensory and hedonic experiences with food. However, for this comparison to be valid, we have to be sure that everyone uses the same ratings to convey the same levels of intensity. Inappropriate scaling methods have become dangerously common in sensory and hedonic research, contributing to many conflicting results and few conclusive answers. Consequently, widespread beliefs about the experiences of obese individuals exist that simply may not be true. Here, we revisit and clarify some of these views using measures that permit valid comparisons. Specifically, we show that obese individuals perceive reduced sweet taste compared to the nonobese – but they like it more, particularly when it is paired with fat. As a result, the obese generally like foods (and sweet-fat foods especially) more than do the nonobese. Individual differences in oral sensation certainly contribute to this effect, but childhood damage to the taste system produces surprisingly similar effects, suggesting a link between childhood disease and long-term obesity risk. These unambiguous results appear only with scales that permit valid comparisons, underscoring the importance of accurate measurement in sensory and hedonic research.
PROTEIN INDUCED INCREASE IN FAT FREE MASS IN ENERGY BALANCE. ; Department of Human Biology, Maastricht University
Background: Protein-rich diets spare fat free mass (FFM) during weight loss and gain FFM at the cost of fat mass (FM) during weight-maintenance thereafter.
Objective: To examine if there is an increase in FFM with a high protein diet in energy balance.
Design: The 4-compartment body-composition of 25 subjects (BMI 22.07±1.71kg/m2) and blood parameters were assessed before and after a 3-months intervention of 2MJ/d supplements of protein, or carbohydrate or fat, as exchange with 2MJ/d of habitual energy intake, thus creating a range in protein intake of 96-203% of individual's protein needs. Protein intake was calculated from 24-hour urinary nitrogen.
Results: On average, subjects were in energy balance and did not change their physical
activity over time. Change in body weight (dBW) ranged between -1.23kg and
+1.93kg. FFM increased by 0.73kg (P=0.033), independently of dBW. Independently of dBW, protein intake explained 24% of variation in d%FFM (P=0.047), while habitual leisure-time physical activity explained 45% (P=0.009). Protein intake
explained 29% of variation in dBMC (P=0.030). FM decreased by 0.34kg. Trunk %FM
was negatively related to protein intake (r=-0.598, P=0.014). Fasting FFA's were positively related to FM and negatively to FFM (r=0.656, P=0.008 and r=-0.556, P=0.013). dHDL concentration was a function of protein intake (r=0.638, P=0.01).
Conclusion: A 50% elevation in protein intake of individual's protein needs increased FFM independently of dBW, with additional positive effects on lipid and bone characteristics.
THE ROLE OF THERMOGENESIS IN ANTIPSYCHOTIC DRUG INDUCED OBESITY . ; 1Monash University, 2Orexigen Therapeutics
Weight gain associated with the use of antipsychotic drugs (APDs) is well recognized in human and in rodent models of APD induced obesity. Our recent studies showed that chronic olanzapine (OLZ) administration causes a maintained increase in body weight despite only a transient increase in food intake with a reduced level of thermogenesis in brown adipose tissue (BAT) making a major contribution to the weight gain.
The aim of the present study is to determine the anatomical substrate which may subserve the change in thermogenesis and body weight. Female rats were administered OLZ acutely (10mg/kg; sc) and elevated levels of Fos protein were assessed in the brains of rats. In order to determine the extent to which these activated neurons were likely to involve descending autonomic pathways to thermogenic endpoints, Fos was combined with the retrograde transport of cholera toxin b (CTb) from the spinal cord. Discrete groups of neurons in a number of hypothalamic and brainstem sites including the lateral hypothalamus (LH) and the locus coeruleus were shown to project to the spinal cord. These studies have been extended to determine the neurochemical phenotype in sites such as the LH, which contains spinally projecting neurons that are Fos and Orexin A positive.
These data collectively show a significant involvement of descending autonomic pathways from the hypothalamus and brainstem that may underpin changes in BAT
activity following OLZ treatment. The challenge remains to further dissect the central
neural pathways that may help to dissociate the weight gaining form the antipsychotic effects of OLZ.
LONG TIME COURSE ADAPTATION OF GLUCOSE METABOLISM TO HIGH PROTEIN FEEDING IN RATS WITHOUT CHANGES IN RESTING ENERGY EXPENDITURE. ; INRA, AgroParisTech, UMR914 Nutrition Physiology and Feeding Control
High protein diet is known to limit adiposity increase in rats principally by decreasing the spontaneous energy intake. We postulated that the modification in energy metabolism and substrates oxidation could be involved in this effect.
Wistar rats were fed a normal protein diet (NP) for 1 week and then a high protein diet (HP) for 1, 3, 6 or 15 d. Gastric emptying, energy metabolism as well as hepatic gene expression of key enzymes involved in energy pathways were studied.
Both fasting total energy expenditure and resting energy expenditure were homogenous among groups. Thermic effect of feeding (TEF) varied only transiently. During fasting, lower CHO oxidation was observed at the expense of protein oxidation. In the fed state, fat oxidation increased after 1 d of HP diet but then decreased after 3 d. Interestingly, CHO oxidation was twice lower after 1 d of HP diet and then slowly increased until 15 d but remained lower than in NP rats. These results are consistent with gene expression encoding hepatic enzymes involved in glycolysis, lipogenesis and glycogen synthesis. Moreover, stomach emptying was transiently delayed in the first 3 days of HP diet.
We concluded that TEF was not responsible for the lower energy intake usually observed in HP rats. In contrast, changes in carbohydrate oxidation and gastric emptying appeared to be correlated with changes in spontaneous intake. Both parameters could act as satiety signals.
OBESE INDIVIDUALS SHOW BLUNTED STRIATAL RESPONSE TO FOOD: RELATION MODERATED BY DRD2 GENE . ; 1Oregon Research Institute, 2University of Texas at Austin, 3University of Oregon, 4Peirce laboratory, Yale University
As dopamine D2 receptor density in the striatum is inversely related to BMI among obese humans and obese rats have lower basal dopamine levels and reduced D2 receptor expression, it has been proposed that people with hypofunctioning reward circuitry overeat to boost a sluggish reward system. We conducted four fMRI studies that tested whether obese humans would show blunted activation of the striatum in response to food. In all studies, obese humans showed reduced activation of the striatum in response to receipt of chocolate milkshake and BMI was inversely related to activation in the striatum. As humans with an A1 allele of the Taq1 A1 DRD2 gene have 30-40% fewer D2 receptors than those without an A1 allele, we next tested whether the relation between obesity and blunted striatal response would be amplified in those with the A1 allele because they have reduced dopamine signaling capacit: the inverse relation of BMI to blunted striatal response to food receipt was amplified in those with the A1 allele. Finally, we tested whether humans with a blunted striatal response to food intake are at increased risk for future weight gain and whether the presence of the A1 allele of the DRD2 gene amplified this relation: the blunted striatal response predict future weight gain over a 1-year follow-up period, but only for those with the A1 allele. Findings collectively suggest that hypofunctioning food reward circuitry increases risk for obesity.
INVOLVEMENT OF PERIPHERAL GLP-1 IN SATIETY, GLYCEMIC CONTROL AND GASTRIC MOTILITY. ; 1Center for Behavior and Neurosciences, University of Groningen, 2Department of Medicine, University of Cincinnati
Glucagon-like peptide-1 amide (GLP-1) is secreted from ileal L-cells, pancreatic A-cells and from nerve terminals in the CNS. In the periphery, GLP-1 is secreted in response to ingested nutrients and is thought to ameliorate fuel excursions associated with ingested food. In the CNS, GLP-1 participates in regulation of ingestion and neuroendocrine outflow. This study investigated whether peripherally produced GLP-1 is able to affect ingestive behavior, gastrointestinal motility, and glucose homeostasis in male wistar rats. Elevated plasma GLP-1 concentration was reached by intragastric infusion of sucrose (S) and acarbose. Acarbose (A) causes dumping of S into the lower intestine (because of inhibiting the lumenal brush border enzyme α-glucosidase) which subsequently increases GLP-1 release into the blood stream. Relative to A alone, S+A had a more profound anorexigenic efficacy than S (without taste aversions), and this was blocked by prior peripheral immunoneutralization of GLP-1 (by i.v. infusion of an antibody raised against GLP-1). While GLP-1-immunoneutralization greatly augmented plasma insulin levels following S but not following S+A, the effect of S+A to inhibit gastric motility was not blocked by GLP-1 immunoneutralization. We conclude that circulating GLP-1 is involved in satiety and glucose disposal, but not in the ileal brake mechanism.
PERSISTENT EFFECTS OF HIGH-INTENSITY SWEETENERS ON BODY WEIGHT GAIN IN RATS. . ; Purdue University
Saccharin-sweetened diets have been shown to increase body weight gain, food intake and adiposity in rats. The present experiments examined the persistence of these effects, and whether Ace-K produced similar effects. Adult male rats were assigned to one of three groups and all received daily access to sweetened or unsweetened yogurt along with chow for 12 days. Yogurt and chow were available for 23 hr per day in the first experiment; in the second experiment yogurt was available for 1 hr per day while chow was unavailable; chow was available for the remaining 23 hr. Each group received 6 days on which the yogurt was unsweetened, and 6 days on which the yogurt was sweetened. For one group, yogurt was sweetened with 20% Glucose, for a second group, 0.3% AceK and for the third group, 0.3% Saccharin. In both experiments, animals given the AceK and Saccharin sweetened yogurt gained significantly more weight than the animals given the glucose-sweetened yogurt. In the final experiment, naive male rats were assigned to Glucose or Saccharin groups, and given access to 30 g yogurt for two weeks as in the first experiment. Yogurt exposure was then discontinued and body weight was monitored for an additional two weeks. Saccharin-exposed animals gained more weight than glucose-exposed animals, and these differences in body weight gain persisted for two weeks following termination of yogurt consumption. These data suggest that the effects of consuming artificially sweetened diets on body weight gain are not specific to saccharin and persist after the discontinuation of the non-predictive sweet taste – calorie experience.
EFFECT OF PACE OF EATING ON WITHIN-SESSION DECREASES IN HUMAN EATING BEHAVIOR BY INSTRUCTING PARTICIPANTS TO CHEW EACH MOUTHFUL OVER 30 TIMES . ; 1Department of Psychology, Graduate School of Letters, Doshisha University, 2Department of Psychology, Faculty of Letters, Doshisha University
Eating slowly has been believed to reduce food intake in behavior therapy of obesity (Stuart, 1967). Therefore, many experimental studies have been done in recent years to validate whether eating slowly actually reduced meal intake. In experimental studies, eating rate was manipulated by a variety of techniques. For example, Spiegel, et al. (1993) manipulated bite size of sandwiches in 3 conditions (5, 10, 15g). However, few studies directly manipulated chewing number of times by instruction. This study examined effects of pace of eating on within-session decreases (transition of pace of eating in eating session) in eating behavior with participants instructed to chew each mouthful over 30 times. All participants were healthy men and session lengths were 20 minutes. The test foods were potato chips. Participants in a slow group ate one potato chip at a time, chewing over 30 times, while participants in a control group were not given an instruction about number of chews. Participants could eat freely and stop eating when they felt full. As a result, the control group ate more at the beginning of the session. However, within-session decreases were steeper in control groups than slow groups. In addition, median of total amount of time was not significantly different in both groups, but total amount of intake was significantly smaller in the slow group than the control group.
POTENTIAL EPIGENETIC MECHANISMS FOR METABOLIC PROGRAMMING BY MATERNAL STRESS AND DIET.. ; 1Johns Hopkins University, 2University of Maryland
The prenatal developmental period is sensitive to environmental peturbations. Our data show that chronic stress or high fat (HF) diet during gestation results in offspring that have impaired glucose tolerance by postnatal day 21 (P21) and are more susceptible to diet-induced obesity in adulthood. Here we examined possible mechanisms for increased metabolic vulnerability. Pregnant Sprague-Dawley rats were maintained on standard chow (CHOW) or 60% HF diet throughout gestation and lactation. Half of each group was exposed to chronic variable stress (STRESS) during the 3rd week of gestation while control dams were left undisturbed (CON). One male was randomly selected from each litter for each postnatal measure. On P14, in situ hybridization showed that Npy expression in the arcuate (ARC) was elevated in pups from dams exposed to STRESS, HF diet or both. Maternal HF diet resulted in decreased paraventricular nucleus (PVN) Crh and ARC Pomc expression and STRESS further suppressed it. By P21, ARC Npy expression was decreased in pups from dams exposed to both STRESS and HF diet, while PVN Crh expression was elevated in the same group. Bisulfite sequencing revealed that CpG dinucleotides within Crh and Pomc in the hypothalamus of P21 pups were differentially methylated among the groups. These data suggest a role for epigenetic mechanisms in the long-term metabolic consequences of maternal stress and diet. Supported by: NIH HD055030, DK077623, MH-15330.
THE RELATIONSHIPS AMONG RESTRAINT EATING, DRIVE FOR THINNESS, AND SENSE OF HEALTH IN JAPANESE UNDERGRADUATE FEMALES. . ; 1Department of Learning Science, Hirhoshima University, 2Department of Psychology
It is said that in Japan, the number with eating disorders in adolescent female is increasing. And it is considered that the number of individuals who is not given a diagnosis of eating disorder but express a problematic eating behavior is increasing. The purpose of this study was to assess eating behaviors (restraint, emotional, and external eating), drive for thinness and sense of health on Japanese normal undergraduate female students. One hundred and nine female college students were participated in this study. They were asked to complete the Dutch Eating Behavior Questionnaire (DEBQ), Contour Drawing Rating Scale (CDRS), Sense of Health Scale, and State-Trait Anxiety Inventory. And they were also asked their height and weight to calculate their Body Mass Index (BMI). Results from Structural Equation Modeling (SEM) showed that the drive for thinness was affected by their BMI. The drive for thinness affected restraint eating. And restrained eating and trait anxiety influenced sense of health. These results indicated that the drive for thinness, which was enhanced by their BMI effects negatively not only their eating behavior, but also their mental health in Japanese undergraduate female students.
NUTRIENT SENSING IN HUMANS: EFFECTS ON VAGALLY-MEDIATED TISSUE RESPONSES, HUNGER AND FOOD INTAKE. ; Monell Chemical Senses Center
Studies conducted in animals suggest that prolonged glucose infusions increased vagal efferent activity through central recognition of elevations in plasma glucose. Prolonged increases in blood glucose could also be expected to induce compensatory decreases in food intake. We conducted a series of studies in lean, healthy control subjects to determine if prolonged elevations in blood glucose and the coincident increase in plasma insulin could alter vagal efferent activity and eating behavior in humans. All subjects underwent, at minimum, two experimental conditions: 1) 48-h saline infusion (50 ml/hr) and 2) 48-h glucose infusion (15% glucose;200 mg/m2/min). Blood samples were drawn and blood pressure and heart rate variability measured throughout the 48-h period. Hunger, satiety and food intake were also monitored. This experimental paradigm results in a metabolic profile resembling an obese, glucose intolerant individual with mild hyperglycemia, hyperinsulinemia and hyperleptinemia. We found that the prolonged glucose infusion did in fact increase vagal efferent activity at the level of the pancreas. In contrast, decreases in cardiac vagal efferent activity were observed Subjects ingested the same amount of food whether saline or glucose was infused. However, despite the absence of compensatory eating behavior, leptin levels were inversely correlated with hunger (R=0.62, p<0.03) under both experimental conditions and strongly inversely correlated with food intake (R=0.79 p<0.003) during the glucose infusion condition. No relationship was observed between plasma insulin or glucose and food intake. These data suggest that central recognition of increases in plasma glucose and possibly insulin can result in altered vagal efferent activity. Furthermore, changes in plasma leptin are also recognized by the brain but more than 48-h may be required to alter eating behavior.
ELEVATED SPONTANEOUS PHYSICAL ACTIVITY AND LEAN MASS GAIN IN OBESITY RESISTANT RATS. ; 1VA Medical Center, 2University of Minnesota, Department of Food Science and Nutrition
Elevated spontaneous physical activity (SPA) is associated with reduced body weight gain in lean children, adults and adult obesity resistant (OR) rats, suggesting that elevated SPA protects against obesity. The relationship between SPA and adiposity during development and maturation in obesity prone (OP) and OR rats is unclear. We sought to characterize the SPA and body composition profile of OP and OR rats during development and maturation, beginning with measurements prior to the onset of obesity in OP rats. We hypothesized that the growth trajectories of body fat and SPA would be inversely related, and that OR rats would have higher SPA, reduced energy efficiency and lower body fat than OP rats. To test this, we measured cumulative caloric intake (3x/week), body weight and body composition (weekly), and SPA (monthly) for 8 months beginning at 1 month of age. At each time point, OR rats had greater SPA, weighed less and had less body fat, indicating an inverse relationship between SPA and body fat. Further, 9 mo. old OR rats had gained significantly less body weight (p <.0001) and fat (p <.01) than their OP counterparts. Total caloric intake was also significantly less in OR rats (p <.001), but OR rats were less energy efficient (fat mass gain/caloric intake; p <.002) and gained more lean mass per gram body weight gain (p <.03) compared to OP rats. These data indicate that elevated SPA is associated with reduced body fat gain and increased lean mass gain and suggest that elevated SPA protects against obesity.
BODY MASS LOSS DURING ADAPTATION TO SHORT WINTER-LIKE DAYS DOES NOT AFFECT FOOD FORAGING OR HOARDING.. ; Georgia State University
Siberian hamsters are a seasonal species that exhibits a wide range of physiological and behavioral alterations depending chiefly upon the photoperiod including a reduction in body mass in short ‘winter-like’ days (SD) of ~25-45%. We previously showed that food deprived hamsters lose body mass and, upon refeeding, increase food foraging and hoarding. Siberian hamsters that have attained their final SD stable body mass do not increase food hoarding. Therefore, it may be that only when body mass is dynamically decreasing, might food foraging and hoarding increase, as it does when they are fasted. Therefore, we asked: Does the initial body mass loss with SD exposure increase food foraging and hoarding? Hamsters were housed in a simulated burrow equipped with a wheel running-based foraging system to deliver food pellets in either long ‘summer-like’ days (LD) or SDs for 8 wk. Food foraging, hoarding and intake were measured daily. Despite a significant reduction in body mass over the 8 wk in SD, foraging and hoarding did not change and food intake showed the normal SD decrease. Hoarding in SDs was significantly decreased compared with hamsters maintained in LDs at weeks 3-6. Therefore, the SD-induced decreased body mass does not trigger increased food foraging or hoarding, unlike other body mass reducing challenges. Funded by NIH R01 DK 78358.
CHOLECYSTOKININ-33 (CCK-33) ATTENUATES SHORT-TERM FOOD FORAGING, HOARDING, AND INTAKE IN SIBERIAN HAMSTERS. . ; Georgia State University
Neurochemicals that stimulate food foraging and hoarding in Siberian hamsters are becoming more apparent, but we do not know if cessation of these behaviors is due to waning of excitatory stimuli and/or the advent of inhibitory factors. Cholecystokinin (CCK) may be such an inhibitory factor as it is physiologically important in decreasing food intake in several species including Siberian hamsters. CCK-33 is the most prevalent form of circulating CCK and its systemic injection in rats decreases food intake, doing so to a greater extent than CCK-8. We found minimal effects of CCK-8 on food foraging and hoarding previously in Siberian hamsters, but have not tested CCK-33. Therefore, we asked: Does CCK-33 decrease normal levels or food deprivation-induced increases in food foraging, hoarding and intake? Hamsters were housed in a wheel running-based foraging system with simulated burrows to test the effects of peripheral injections (1 ml) of CCK-33 (13.2, 26.4, or 52.8 µg/kg body mass), with or without a preceding 56 h food deprivation. The highest dose of CCK-33 caused large baseline reductions in all three behaviors for the 1st h post injection compared with saline; in addition, the medium CCK-33 dose was sufficient to curtail food intake and foraging during the 1st h. In food deprived hamsters, the highest CCK-33 dose decreased food intake and hoarding almost completely compared with saline controls. Therefore, CCK-33 appears to be a potent inhibitor of food intake, hoarding, and foraging in both ad libitum and food deprived hamsters. Funded by NIH R01 DK 78358.
PROTEIN-INDUCED SATIETY. ; AgroParisTech, INRA, UMR914
Dietary protein generates signals involved in the induction of satiety. They associate amino acids, gut neuropeptides and hormones acting on specific area involved in the control of food intake in the brain either through vagus-mediated pathways as well as directly after their release in the peripheral blood. Protein infused in the duodenum are able to generate vagal afferent activation in the rat, mainly through a cholecystokinin -dependent mechanism. Amino acid sensors in the hepato-portal region were also shown to modulate the activity of hepatic vagal afferent fiber. Ingestion of protein activates Fos more than other nutrients in the Nucleus of the Tractus Solitarii through a vagus-mediated pathway. This is associated to the activation of noradrenergic/adrenergic pathway known to be involved in cholecystokinin-induced satiety. In contrast there is no activation of the glucagon like peptide 1 (GLP-1) pathway, which is triggered during aversive-induced anorexia. Ingestion of protein also activates satiety pathway in the Arcuate Nucleus of the Hypothalamus, characterized by an up-regulation of the melanocortin (α-MSH containing neurons) POMC pathway and a down-regulation of the neuropeptide Y NPY pathway. Amino acid sensitive neurons have been detected in the lateral hypothalamus (LHA). A critical role for peptide YY in protein-mediated satiation and body-weight regulation has also been proposed. A central role for hypothalamic neuronal AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) have also been proposed in protein-induced satiety. Lastly protein induced lower activation of GABA and opioid neurons by a protein meal in the accubens nucleus.
IN VITRO EVIDENCE OF A COMPUTATIONAL MODEL FOR SWITCHING BETWEEN INGESTION AND REJECTION. ; 1Ohio State University, 2Pennington Biomedical Research Center, 3Ohio State Univeristy, Dept of Mathematics
The lower brainstem contains the neural circuitry to switch between oromotor patterns of ingestion (licking) and rejection (gaping) based on taste. We have developed a computational model of this switching mechanism using Hodgkin Huxley formalism and 3 classes of pre-oromotor neurons (Venugopal et al., 2007). We now present data in support of this model using calcium imaging and whole-cell patch clamp recording from identified pre-oromotor neurons in the reticular formation (RF) to show that disinhibition is a viable mechanism for amplitude changes between licks and gapes. The infusion of GABAA antagonists increased the magnitude of Ca++ flux from RF neurons in response to electrical stimulation of the rostral (gustatory) solitary nucleus (rNST) in a slice preparation. Whole cell patch clamp recording further revealed inhibitory currents in RF neurons that were suppressed by rNST stimulation concomitant with increased excitatory currents in the same cell. We further demonstrated both mono- and polysynaptic excitatory currents in RF cells from rNST stimulation that might initiate licking behavior, and polysynaptic GABAA inhibitory currents. The model predicts that differences in the decay kinetics of two inhibitory neurotransmitters such as those found between GABA and glycine can change the EMG pattern from licks to gapes, and we are presently exploring the effects of glycine on identified neurons in vitro.
Supported by DC00417 (JBT) and NSF DMS0514356 (DT)
FUNCTIONAL STUDIES OF BRAINSTEM TASTE PROCESSING. ; Ohio State University
The rostral nucleus of the solitary tract (rNST) is the initial central site for processing sensory information from the upper GI tract. These signals derive from the chemical constituents, temperature, and texture of ingesta, stimulate oral receptors, activate cranial nerves, and initiate a topographically organized pattern of activity in rNST. There is a rostral-to-caudal orotopy and a lateral-to-medial organization but also ample convergence in the nucleus. The chemosensitive response profiles of taste neurons are highly varied and strongly related to receptive field. Neurons with input from the posterior mouth are more likely to be responsive to bitter-tasting chemicals, narrowly tuned, and lack projections to the waist area of the parabrachial nucleus, suggesting roles in reflexive or hedonic processing. Both neurophysiology and Fos immunostaining indicate a medial chemotopy for the bitter quality, but the 2 techniques are out of register, with the neurophysiological studies suggesting a more lateral distribution than the Fos results. Furthermore, when microstimulation is used to specifically activate different rNST regions, the caudal/medial area with the densest bitter-Fos immunostaining is only weakly effective in eliciting oral motor behavior compared to more lateral sites. The proximity of caudal/medial bitter-Fos neurons to Nos neurons in the dorsal motor nucleus of the vagus suggests a possible role for the caudal/medial rNST in cephalic phase reflexes. This hypothesis is supported by recent Fos experiments demonstrating that fat ingestion activates neurons in this same area. Supported by NIH RO1DC00416 & DETE014320
GLOSSOPHARYNGEAL NERVE TRANSECTION DECREASES DAILY INTAKE OF CORN OIL, CARBOHYDRATE SOLUTIONS, AND GLYCINE. ; Dept. of Psychology & Program of Neuroscience, Florida State University
Although glossopharyngeal nerve transection (GLX), which supplies sensory innervation of the posterior tongue accounting for 60% of the total oral taste buds, attenuates unconditioned gaping to quinine, it appears to have no effect on taste discrimination performance, and has minor effects on unconditioned licking to tastants in brief-access tests. Thus the role of the GL in taste function remains to be comprehensively understood. Here, we report that GLX significantly decreased intake, but not preference, of glucose in 23-h 2-bottle tests (vs. water). This was also observed for other sugars as well as Polycose and glycine, but not for Na-saccharin, NaCl, MSG or L-serine. As previously shown with sucrose, GLX did not alter concentration-dependent licking responses to glucose in a brief-access test. Without influencing immediate affective taste responses, GLX appears to decrease an excitatory signal that competes with postingestive inhibitory signals; a competition that normally promotes carbohydrate solution (and glycine) ingestion. GLX caused an even more striking decrease in corn oil intake as well as preference in 23-h 2-bottle tests. Drinking pattern analysis revealed that GLX rats had a significantly lower bout lick rate to corn oil compared to controls. Thus for corn oil, in addition to reducing a signal that competes with postingestive inhibition, GLX may modulate the hedonic characteristics of the stimulus. Histological verification of the transection is in progress. Supported by R01-DC01628.
NIGHT EATING SYNDROME IN BARIATRIC SURGERY PATIENTS. ; St. Luke's Hospital, Columbia Univ.
Bariatric surgery is the most effective treatment for long term weight loss in obese patients. Yet, it is unclear which eating behaviors influence weight loss in these patients. A primary aim was to determine the effects of the night eating syndrome (NES), and a secondary aim was to assess changes in NES and related eating behaviors one month post surgery. 122 obese (BMI=48.8±8.4 SD), relatively healthy participants (age=40.4±12.8), completed the Dutch Eating Behaviors Questionnaire (DEBQ) subscales concerning external eating and restrained eating; the Emotional Appetite Questionnaire (EMAQ); and the Night Eating Diagnostic Questionnaire (NEDQ). Night eaters (NE, n=51) reported significantly more external eating (F=10.1; p=.002) as well as less restrained eating (F=3.8; p=.05), than non-night eaters (nonNE, n=71). Neither gender nor type of planned surgery (Rouen-y Gastric Bypass or Lap Band) could account for these differences. No differences were found in emotional eating. One month post-surgery, night eating improved (F=3.9; p =.05), and there was no significant difference in restraint or external eating. There was no significant difference in mean weight loss between NE groups, 13.9kg±4.8 for NE and 11.5kg±5 for nonNE. The results showed that in a bariatric surgery sample, night eating is associated with external and restrained eating preoperatively, and that 1month post surgery NES improves significantly, which may explain why there was no longer a difference in restraint or external eating between groups.
OLANZAPINE-INDUCED WEIGHT GAIN . ; Rudolf Magnus Insitute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht
Olanzapine is an effective atypical antipsychotic drug, used in the treatment of
schizophrenia and bipolar disorder. Unfortunately, significant weight gain is a common side effect, as well as dyslipidemia and hyperglycemia. These side effects compromise patient compliance and increase the risk for cardiovascular disease. Olanzapine has affinity for multiple receptors, including dopamine D2, 5-HT2A and 2C, histamine H1, alpha-adrenergic and muscarinic receptors. Many of these receptors play a role in the regulation of feeding behavior and/or energy balance, however, so far it is not completely understood which of these receptors are involved in olanzapine-induced weight gain.
To enable the development of novel antipsychotics that are equally therapeutically effective but less prone to cause weight gain, it is crucial to gain insight into the mechanisms involved in olanzapine-induced weight gain. We, therefore, developed an animal model, using male Wistar rats, to study in detail the effects of this drug on feeding patterns, food preference, locomotor activity and body temperature. Our preliminary results indicate that olanzapine markedly reduces spontaneous locomotor
activity and induces mild hyperphagia. After having identified further the effects of olanzapine administration on different aspects of energy balance we plan to use this model to identify the receptors responsible for each of these effects.
REGULATION OF ENERGY BALANCE IN MICE SELECTIVELY BRED FOR HIGH VOLUNTARY ACTIVITY. ; 1Center for Behavior and Neurosciences, University of Groningen, 2Dept Biology, University of California, 3Aberdeen Centre for Energy Regulation and Obesity, School of Biological Sciences, University of Aberdeen
Maintenance of high spontaneous activity levels is probably a key mechanism to prevent high-fat diet-induced obesity and the associated metabolic syndrome in humans. In the attempt to assess these interactions in an animal model, we subjected mice selectively bred over 30 generations for high and normal voluntary wheel running behavior to normal chow or a 60% high fat diet. Compared to controls, selected females, and to lesser extent males, weighed less, had less body fat, but elevated plasma adiponectin, and were more active even without running wheels. Energy expenditure and resting metabolic rate were increased in selected mice relative to controls, particularly in females. Food intake was increased, particularly during the relative inactive light phase in selected mice. When animals were switched to a high-fat diet, control mice rapidly increased body weight, associated with a reduction in food intake indicating increased food efficiency. Selected females, and to a less extent selected males, were entirely diet-induced obesity resistant, had increased food intake, and energy expenditure. Since selected - but not control - mice preferred high-carbohydrate food above the high-fat diet in a food preference test, the increased fat intake in selected animals is probably a non-favoured, but necessary response to maintain energy balance.
EFFECTS OF SOYPROTEIN ALONE OR AS PART OF A MEAL ON THE SOMATOTROPIC AXIS. ; 1Dept. of Human Biology, Maastricht University, 2TIFood and Nutrition
Growth hormone(GH) is an important regulator of growth and body composition. It has been shown that GH- release can be promoted by intravenous or oral administration of various single amino acids(AA), either alone or in combination. The effects of dietary protein on GH-secretion, however, are less well described.
The effects of dietary protein on GH-secretion are investigated in two different studies: firstly, we compared oral ingestion of hydrolysed soy protein and complete soy protein with an AA-mixture(reflecting the AA composition of soy protein) and, secondly, we compared ingestion of a complete meal containing soy protein as the sole protein source with soy protein alone. Both studies were performed in eight healthy women(age:19-36y, BMI:19-26 kg/m2) in a randomized single blind, placebo-controlled crossover design. Serum GH was determined every 20 min during 5 h.
Ingestion of the complete soy protein, hydrolysed soy protein and the AA-mixture all increased plasma GH-responses (either by area under the curve or peak values) to a similar extent, when compared with placebo(p<0.05). The GH-responses to ingestion of soy protein(p<0.05 versus placebo) were completely abolished when soy protein was ingested as part of a complete meal.
In conclusion, ingestion of soy protein, either hydrolysed or intact, as well as amino acids reflecting soy protein stimulates GH-release to a similar extent. This effect, however, is not present when soy protein is ingested as part of a complete meal, suggesting that other macronutrients counteract the somatotropic actions of soy protein.
ASSOCIATION BETWEEN DIETARY ARGININE AND LYSINE INTAKE AND 6Y-CHANGE IN BODY COMPOSITION AMONG 9Y OLD CHILDREN (EYHS). ; 1Dept. of Hum Bio, 2TIFood&Nutri, 3Inst for Prev Med
Growth-hormone(GH) improves body composition, by increasing lipolysis, protein syntheses and secretion of insulin-growth-factor-1(IGF-1), resulting in a reduced fat mass and increased fat free mass. The amino-acids arginine(ARG) and lysine(LYS) are stimulators of GH.
This study examined associations between intakes of ARG, LYS and 6y change(∆) in body-composition(BC) among 364 9y old children. Data were collected from Odense Country Denmark, during 1997-8 and 6y later as part of the European Youth Heart Study. We divided boys and girls into normal-weight and overweight, based on BMI quintiles. BC among children was subdivided by fat free mass index(FFMI) and fat mass index(FMI). Associations between ARG, LYS and ∆FFMI and ∆FMI were analysed by multiple-linear-regressions. Among girls inverse associations were found between both ARG and ∆FMI(β=-1.12±0.60 p=0.04) and LYS and ∆FMI(β=-1.13±0.51 p=0.03), suggesting that high intake of both amino acids were associated with less gain in fat-mass. For the overweight girls, when LYS was high, ARG was directly associated with ∆FFMI(p=0.04) whereas when LYS was low, ARG seemed to result in an impaired development of fat free mass. This same tendency was also found among normal weight girls and boys.
In conclusion, among children high intakes of both ARG and LYS may prevent body-fat gain; and when high ARG is combined with high LYS, it may stimulate increase of fat-free mass.
AGOUTI-RELATED PROTEIN (AGRP) INTO THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS (PVH) INCREASES FOOD HOARDING, FORAGING AND FOOD INTAKE IN SIBERIAN HAMSTERS.. ; Department of Biology, Georgia State University
Humans and other animals forage for food and subsequently hoard food in anticipation of or in preparation for depleted food stores or alternatively simply for later consumption. AgRP, a melanocortin 3/4 receptor (MC3/4R) inverse agonist, stimulates food intake given in the 3rd ventricle or in the PVH in rats. In Siberian hamsters, 3rd ventricular AgRP increases foraging, food intake and especially food hoarding. Central melanotan II (MTII; a MC3/4R agonist) attenuates both ad libitum and post food deprivation-induced increases in food intake in rats and Siberian hamsters, and to a lesser extent hoarding/foraging. We therefore tested the effects of site-specific PVH injections (200 nl) of AgRP (25, 50, 75 pmol) and secondly, of MTII (0.05 nmol) after a 56 h fast on
foraging, hoarding and/or food intake This was accomplished in hamsters housed in wheel running-based foraging system with simulated burrow housing. AgRP increased food hoarding 2-4 h post injection and also increased food intake and foraging 2 d post injection vs. the vehicle control. MTII after the fast did not significantly attenuate these behaviors. Although these results suggest that inverse agonism of PVH MC3/4Rs stimulate foraging/hoarding and food intake (AgRP data), MTII into the PVH, at the dose tested, does not result in reciprocal changes in these behaviors. Funded
by NIH R01 DK 78358.
A BREAKFAST WITH A-LACTALBUMIN, GELATIN, OR GELATIN+TRP LOWERS ENERGY INTAKE COMPARED WITH A BREAKFAST WITH CASEIN, SOY, WHEY, OR WHEY-GMP . ; Maastricht University, TIFN
Background: Dietary protein plays a role in body weight regulation, partly due to its effects on satiety.
Objective: To compare the effects of casein-, soy-, whey, whey without glycomacropeptide(GMP)-, a-lac-, gelatin, or gelatin with tryptophan(TRP) (added to the level present in a-lac)- protein breakfasts in 2 concentrations on subsequent satiety and energy intake (EI).
Design: 24 healthy subjects (mean+SEM BMI:24.8+0.5 kg/m2; age:25+2 yrs) received a subject-specific standardized breakfast; a custard with either casein, soy, whey, whey-GMP, a-lac, gelatin, or gelatin+TRP as protein source with either 10/55/35(normal) or 25/55/20(high)En% protein/carbohydrate/fat in a randomized, single-blind design. The sensitive time-point for lunch, determined in advance, was after 180 min; subjects were offered an ad lib lunch. Appetite profile (Visual Analogue Scale,VAS) and EI were determined.
Results: At the level of 10En% and 25En% from protein, EI at lunch was ~20% lower after an a-lac or gelatin(+TRP) breakfast (2.5+0.2 MJ) compared with after a casein, soy, or whey-GMP breakfast (3.2+0.3 MJ,p<0.05). Appetite ratings at 180 min differed 15-25mm (~40%) on a 100mm VAS (p<0.05). Differences in EI were a function of differences in appetite ratings (R2=0.4,p<0.001).
Conclusion: Different proteins a-lac, gelatin, gelatin+TRP) that are 30-50% more satiating than other proteins (casein, soy, whey, whey-GMP) induce a related 17-24% reduction of subsequent energy intake.
LEPTIN SIGNALING IN MIDBRAIN DOPAMINE NEURONS REGULATES (HYPER)ACTIVITY DEPENDING ON NEGATIVE ENERGY BALANCE. ; Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht
Excessive physical activity and reduced food consumption are commonly described as symptoms of anorexia nervosa. Hyperactivity in anorectic patients has been associated with low plasma leptin levels. The adiposity hormone, leptin, targets several areas of the brain including the hypothalamus and hindbrain. Recent data identified leptin receptors on dopamine neurons of the ventral tegmental area (VTA) in rats. Dopamine neurons in these regions are key components of feeding and locomotor activity. Activity-based anorexia (ABA) is considered as an animal model for AN. The ABA model consists of scheduled feeding (1-1.5 hour food access at the beginning of the dark phase) in combination with voluntary wheel running, which results in severe body weight loss and increased physical (hyper)activity. It is known that leptin reduces hyperactivity and food intake when rats are exposed to the ABA model. In this study, we investigate the involvement of the VTA during (hyper)activity and feeding regulation during ABA. VTA leptin injections significantly reduced running wheel activity in comparison with vehicle injections. Food intake and body temperature remained unchanged. These data show that the VTA plays an important role in (hyper)activity during negative energy balance, but is not involved in the regulation of body temperature. In addition, it supports a role of the VTA in the connection of hyperactivity and energy balance.
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MATERNAL OBESITY LEVELS AT WEANING ARE INFLUENCED BY THE PUPS&RSQUO; STRAIN: INSIGHTS FROM A CROSS-FOSTERING STUDY IN OLETF RATS. ; 1Bar-Ilan Univ, 2Johns Hopkins Univ
The OLETF rat is a model of hyperphagia induced obesity. OLETF pups are heavier than their LETO controls at birth and are hyperphagic throughout lactation. We used cross-fostering to assess the influence of pups’ genotype on dams’ obesity levels at the time of weaning. Dams’ body weight was measured from first pregnancy day until weaning every fifth day and intake was assessed daily. Pups were switched between or within strains or left untouched on postnatal day 1. At the end of the third postnatal week, a nursing test was performed. At weaning, the dams were sacrificed and blood plasma and three different fat pads were collected and weighed. Results: LETO dams appear not to be influenced by the strain of the pups, and presented similar physiological parameters at the time of weaning, when raising pups of both strains. In contrast, OLETF females were strongly influenced by the pups’ strain: raising "genetically lean" offspring induced them to accumulate greater amounts of fat, and to present increased body weight and leptin levels, despite normal intake levels during lactation. Both OLETF and LETO dams presented equal nursing duration when raising pups from the opposite strain: significantly longer than that observed in the LETO controls, but significantly shorter than usually observed in the OLETF strain. Thus, it seems that the strong interaction observed between the mother and her offspring is necessary in order for the OLETF dam to present reduced obesity levels at the time of weaning.
Support: NIH/NIDDK – RO1 DK57609
BINGE EATING STATUS INFLUENCES PRE-DIET WEIGHT CHANGE AND TEST MEAL INTAKE IN OBESE INDIVIDUALS. ; 1NY Obesity Research Center, St. Luke's Roosevelt Hospital, Departments of Medicine and Psychiatry, 2, Columbia University
Our aim was to test the influence of binge eating status weight change and test meal intake prior to the start of a liquid formula diet program. Body weight in 58 obese S’s (11M, 47F; BMI=38.5±8.0) was measured at an initial consultation (Day 1) and again 1 day prior to starting a liquid formula diet (Day 2; mean interval 19.9d±19.8 SD). From the Questionnaire on Eating and Weight Patterns (QEWP-R), 24 participants were classified as binge eaters (BE) and 34 as not (NB). On Day 2, participants consumed a nutritionally complete liquid test meal (Boost 1:1 water, 0.5kcal/g) by straw from a concealed container until extremely full. Baseline weight on Day 1 did not differ, t=0.64, p=.95, between BE (108.2 kg ±20.3) and NB (107.7 kg ±30.7) ANOVA indicated that BE participants lost weight (-0.6±1.7 kg;) by Day 2, while the NB participants gained weight (+0.7±5.8kg;), with significant differences by group in weight change per day (p=.039). Test meal intake was greater for BE (755kcal ±401, than NB (702kcal ±384; F=6.1, P=.02). Weight change and test meal intake were unrelated (r =.048, p =.722). Weight gain in the NB group may be attributable to a ‘last supper’ phenomenon prior to caloric deprivation (Eldredge, Agras & Arnow,1994), and weight loss in the BE group to reduced binge eating prior to starting a treatment program.
PROTEIN INTAKE, SATIETY AND BODY-WEIGHT REGULATION . ; 1Maastricht University, 2TIFood and Nutrition
Recent findings suggest that protein intake seems to play a key role in body-weight management, through increased satiety, wherein different proteins show different satiating efficiences, and through its effect on thermogenesis, body composition and energy inefficiency. The different satiating effects appear as significant differences in subsequent energy intake during a testmeal, and even beyond. Protein-induced satiety and subsequent energy intake is related to, or synchronized with, thermogenesis, elevated amino-acid concentrations, or elevated anorexigenic hormone concentrations. Long term protein induced body-weight loss and body-weight maintenance are supported by satiety,
thermogenesis, body composition and energy inefficiency. Increased insulin
sensitivity may occur but it is unclear whether this is due to weight loss or
type of diet. Since protein intake is studied at different energy intakes, absolute and relative protein intake needs to be discriminated. In absolute terms (grams per day), a normal protein diet becomes a relatively high protein diet if combined with diet-induced negative energy balance and at subsequent weight maintenance. Therefore, 'high protein diet-induced negative energy balance diets' aim to keep the grams of protein ingested at the same level as consumed during energy balance, before body-weight loss.
CHRONIC CENTRAL INFUSION OF AMYLIN LOWERS BODY WEIGHT GAIN INDEPENDENT OF INITIAL BODY WEIGHT IN CHOW FED RATS BUT NOT IN RATS AFTER 3 WEEKS OF ENSURE® FEEDING. . ; 1Inst. Veterinary Physiology, Univ. Zurich, 2Dep. Psychiatry, Univ. Cincinnati
Amylin (AMY) shares characteristics of adiposity signals. Here we investigated central AMY’s effects on body weight (bw) gain in rats. Two groups of rats (F) received either a 14 day chronic intra-3rd ventricle infusion of AMY (2 pmol/h) or saline (SAL). They were fasted for the first two days and then refed ad libitum. Two additional groups (AL), AMY or SAL, were fed ad libitum from day 0. Both F-groups lost ~40g due to fasting. After refeeding, SAL-F rats regained bw and reached the same level as SAL-AL rats. AMY-F regained bw to the same level as AMY-AL, which also had lost ~20 g in 3 d initially. Bw of AMY treated rats was significantly lower than SAL treated rats. This indicates that central levels of AMY influence the bw to be maintained. The setup of the second experiment was similar, but before infusion with AMY or SAL, half of the rats were overfed for 3 weeks with Ensure® to increase their bw ~60g above that of chow-fed rats. At the time of implantation of minipumps, all rats received chow only. AMY-chow significantly lost bw compared to SAL-chow. Surprisingly, AMY-overfed maintained bw to the same level as the SAL rats, suggesting amylin insensitivity. Taken together, these data provide support for amylin to act as adiposity signal. However, after exposure to high energy diet Ensure®, rats appeared to develop an insensitivity to central amylin infusion. The underlying mechanisms are currently being explored.
EFFECT OF PERIPHERAL AND CENTRAL AMYLIN ON ENERGY EXPENDITURE AND BODY TEMPERATURE.. ; Inst. Veterinary Physiology, Univ. Zurich
Amylin is involved in the regulation of meal ending satiation. It also shares typical features of adiposity signals. Last year we presented that acute peripheral injection of amylin’s agonist salmon calcitonin stimulates energy expenditure (EE). Here we investigate the effect of chronic peripheral amylin administration on EE.
Rats received an osmotic minipump (sc) containing either amylin (2 μg/kg/h) or saline. A third group of rats received saline, but were yoke fed to amylin treated rats to control for the altered food intake by amylin. Although there was no effect of amylin on EE compared to saline ad lib, EE tended to be increased compared to a yoke fed control group on the first 3 days of infusion. Light phase body temperature was significantly increased on days 1,3 and 4 compared to yoke fed. These data suggest that amylin prevents the compensatory decrease of EE due to reduced food intake.
Since amylin’s action occurs in the brain, we also investigated the effect of centrally injected amylin (2 or 10 pmol i3vt) on EE. Amylin was injected in the middle of the light phase in rats that had no access to food for 3 hours. Amylin (10 pmol) strongly increased EE compared to saline (7.3 ± 0.2 vs 5.9 ± 0.1 kcal/kg/h) and body temperature (~1°C increase vs saline) the first hour after injection, whereas 2 pmol of amylin had no significant effect. These data indicate that amylin probably influences EE through a central mechanism. Further studies will investigate this mechanism and the chronic effect of central amylin.
HINDBRAIN LEPTIN RECEPTOR STIMULATION ENHANCES THE ANOREXIC RESPONSE TO CHOLECYSTOKININ . ; 1VA Puget Sound Health Care System, 2Department. of Medicine, University of Washington
Leptin is thought to reduce food intake in part by increasing sensitivity to satiety signals such as cholecystokinin (CCK). It is established that forebrain leptin action can augment both the anorexic and hindbrain neuronal activation responses to CCK. Because caudal brainstem leptin receptor activation also reduces food intake, we hypothesized that hindbrain leptin treatment would enhance the response to CCK. First, we determined that 4th-icv leptin injection prior to IP CCK treatment significantly reduced short-term chow intake, whereas either treatment alone had no effect. Next, to identify specific hindbrain nuclei in which leptin may act to augment CCK-induced anorexia, we targeted leptin injections directly at the dorsal vagal complex (DVC). When rats received intra-DVC leptin plus IP CCK, at doses subthreshold for effects when delivered alone, we observed a significant decrease in food intake. We then asked whether hindbrain leptin treatment also enhances the hindbrain c-Fos response to IP CCK. We found that 4th-icv leptin injection had no effect on CCK-induced c-Fos in the nucleus of the solitary tract, in surprising contrast with the c-Fos-enhancing effect of forebrain leptin pre-treatment. We conclude that leptin receptors in multiple brain regions can modulate the response to CCK, but the neural circuitry that mediates these interactions may differ depending on which leptin receptor-expressing neuronal populations are engaged.
BLOOD GLUCOSE CHANGES FOLLOWING THE INGESTION OF SUCROSE- AND ASPARTAME-SWEETENED BEVERAGES. ; Wittenberg University
The purpose of the present study was to examine the blood sugar response to sucrose-sweetened and aspartame-sweetened beverages. Sixty-four fasted participants were randomly assigned to drink one of four liquids: Sprite®, Diet Sprite®, apple juice, or water. After the baseline blood-glucose level (BGL) measure, each subject was shown the distinctively labeled bottle containing their assigned beverage and then given 8 oz of the beverage to drink in two minutes. Their BGLs were measured 5, 10, and 15 min post-consumption. No significant differences in BGLs were detected among the groups at baseline. At 5, 10, and 15 min post-consumption, significantly higher BGLs was observed in the Sprite group compared to the other groups. No differences were found between any of the other groups at any time. A significant Time X Group interaction was detected, with BGLs increasing over the 15 minutes in the Sprite and apple juice groups but not in the water and Diet Sprite groups. No significant differences were found between the BGLs for any of the groups five minutes post-consumption and at baseline. Ten minutes post-consumption, the BGLs of the Sprite group were significantly higher than baseline. Fifteen minutes post-consumption, BGLs of the apple juice and Sprite groups were significantly higher than their respective baselines. This study revealed that only sucrose-sweetened beverages had significant effects on blood glucose. In the present experiment, apple juice but not Diet Sprite had similar effects to Sprite, although the effect was weaker and slower to develop.
VARIED EXERCISE INTESNTIY AND THE EFFECTS ON APPETITE AND FOOD CONSUMPTION IN LEAN YOUNG WOMEN. . ; Norwich University
Exercise energy expenditure (EEE) has previously been shown to suppress hunger ratings and food intake. Purpose: Investigate the effects of low (LOW) and high-intensity (HIGH) exercise on ratings of appetite, time to request the meal, and compensatory food consumption (CFC). Hypothesis: Dose-dependent ↑ in exercise intensity will be associated with ↓ in ratings of appetite during and immediately after exercise, longer time before request of a meal, and no↑in the amount of food intake despite EEE.
Eight women, ages 18-34 years, BMI 20-25 kg/m2, underwent 3 trials: sedentary (SED), and a LOW and HIGH (exercise 40% and 80% of VO2peak with EEE ~ 400 Kcal). An ad libitum meal was offered upon request to assess CFC of the EEE, which was measured by indirect calorimetry. Ratings of appetite were obtained using a visual analog scale every 30 min. Food was measured before and after eating in order to assess CFC.
Exercise ↓hunger. There was a dose-dependent ↑ in CFC, as subjects ate significantly more calories during the HIGH trial as compared to the SED but no difference between the LOW and the other 2 conditions. There was a significant difference in the time to request a meal in LOW vs. HIGH exercise conditions, but no difference between the SED vs. either exercise condition.
LOW and HIGH exercise ↓ hunger during the exercise period. The effect was not long-lasting and subjects ate more Kcals at the ad libitum meal during the exercise trials, but did not make-up the EEE. Contrary to the hypothesis, there was no difference in the time to request a meal between the SED and HIGH, but was later in LOW.
NO EFFECT OF CATECHOLAMINES ON APPETITE AS A RESULT OF VARIED EXERCISE INTENSITY. . ; 1Division of Kinesiology, 2Department of Internal Medicine, The University of Michigan
It is still unclear if catecholamines (NE and E), released with↑intensity of exercise, are related to↓appetite in acute situations. Hypotheses: exercise intensity will result in ↑plasma NE and E and be associated with dose-dependent ↓hunger during exercise; no changes in compensatory food consumption (CFC) at the end of the day despite a substantial outflow of exercise energy expenditure (EEE).
Ten postmenopausal women age 57.2 + 1.8 years, BMI of 23.4 + 0.6 kg/m2, underwent a sedentary and 2 exercise trials (2x/day, at 8 and 14h, with EEE of ~500 Kcals each). Low-intensity trial: ten 15-min exercise bouts at 40% of VO2peak separated by 5-min rest. High-intensity trial: ten 7.5-min exercise bouts at 80% of VO2peak separated by 10-min rest. Equal-sized meals were provided at 7, 13, and 19h. Ad libitum snack offered at 21h to assess end-of day CFC of the EEE. EEE was measured by indirect calorimetry. NE and E were measured in plasma samples collected around the meal and exercise periods. Ratings of appetite were obtained at hourly intervals.
There was a significant and equal suppression of ratings of hunger during the 2nd exercise bout at both intensities. CFC did not differ among the 3 trials despite a1000 Kcal EEE. Both exercise intensities ↓appetite to the same extent while↑NE concentrations occurred with↑exercise intensity in a dose-dependent fashion indicating no relationship. A large EEE is not consciously detected and is unaffected by exercise intensity in postmenopausal women.
THE MODELING EFFECT ON WOMEN&RSQUO;S EATING: A STUDY OF THE INHIBITORY NORM HYPOTHESIS. ; 1Department of Psychology, Graduate School of Letters, Doshisha University, 2Department of Psychology, Faculty of Letters, Doshisha University
The modeling effect on eating means that people eat more when their eating companions eat more, and they eat less when their companions eat less. Herman, Polivy, & Roth (2003) proposed the inhibitory norm hypothesis and attempted to explain why the modeling effect occurs. This hypothesis assumed that people attempt to monitor others' (models') consumption roughly and eat less than the others in order to avoid being seen by others as eating excessively. Herman et al. (2003) supposed that this phenomenon applies only to palatable foods.
In the present study, we used a fictional participant’s leftover food as the remote model and verified the inhibitory norm hypothesis. We gave our real participants the information that the (fictional) participant’s leftover chocolate cookies were 4 (the big eater condition) in number, or 20 (the small eater condition). We also manipulated appropriateness of the remote model. Some participants were led to believe that the remote model’s fasting duration was the same as their own (the appropriate condition) and the other participants were told that it wasn’t the same (the inappropriate condition). After that, we set up a tasting test for 10 minutes and asked the participants to eat chocolate cookies freely and rate them. In the appropriate condition, we could see the modeling effect. On the other hand, this effect was not visible in the inappropriate condition. These results supported the inhibitory norm hypothesis.
OLFACTORY CONDITIONING REINFORCED BY SACCHARIN IN HUMANS: INFLUENCE OF PROP TASTER AND SWEET LIKER STATUS. . ; 1Department of Psychology, University of Sussex, 2School of Psychology, University of Newcastle
Repeated retronasal exposure to novel food odours with sweet and bitter tastes can lead to subsequent changes in orthonasal liking and sensory experience of the taste-paired odours. PROP tasters have been reported to rate low concentrations of saccharin as more bitter and less sweet than do PROP non-tasters. We therefore predicted that acquired liking for, and sweetness and bitterness of, odours conditioned by association with saccharin would vary depending on PROP taster status. 87 volunteers evaluated two novel odours before and after co-experience of one odour with 4mM/l saccharin and the second with water. PROP taster status was assessed from the intensity of 3.2mM PROP relative to 1.0M NaCl, and sweet-liker status from liking ratings for 0.21 and 0.83 M/L sucrose and 0.0004M/l and 0.0010M/l saccharin. Liking for the saccharin-paired odour increased in sweet likers but decreased in sweet-dislikers. Overall liking change also varied with PROP taster status, with both odours rated less pleasant post-training in the super-taster and taster but not non-taster groups. The saccharin-paired odour was rated sweeter post-training, regardless of PROP taster or sweet-liker status. PROP super-tasters rated the saccharin-paired odour as more bitter post-training, in-line with enhanced bitterness of saccharin in this group. These data confirm that sensory and hedonic changes operate independently olfactory conditioning, and are influenced by individual differences in sensitivity to bitter and sweet stimuli.
HEIGHTENED RESPONSES TO THE HEDONIC QUALITIES OF SUCROSE IN OLFACTORY CONDITIONING FOR WOMEN SCORING HIGH ON THE THREE FACTOR EATING QUESTIONNAIRE DISINHIBITION SCALE. . ; Department of Psychology, University of Sussex
In flavour-flavour learning (FFL), repeated co-experience of a novel flavour and a hedonically valanced flavour can lead to changes in liking for the novel flavour. Some studies suggest that restrained eaters are insensitive to FFL, while disinhibited eaters may over respond to hedonic stimuli. Here we assessed FFL through associations between food-related odours and sweet and bitter tastes to explore further how eating attitudes influence FFL. 52 women, pre-selected to be high or low on the restraint and disinhibition factors from the Three Factor Eating Questionnaire (TFEQ), evaluated 2 novel odours orthonasally before experiencing retronasal pairings of one odour with sucrose and the second with quinine before orthonasal re-evaluation of the odours. At post-training, overall liking increased for the sucrose-paired odour but this effect was greater in women with high scores on the TFEQ disinhibition factor. Liking for the quinine-paired odour decreased equally in all groups. The sucrose-paired odour was rated as sweeter, and quinine-paired odour more bitter at post-training and these acquired sensory qualities were unaffected by restraint or disinhibition factors from the TFEQ. Overall, these data found no evidence of impaired FFL in restrained women, but instead found greater responsiveness to hedonic qualities of sucrose in women scoring high on the disinhibition factor, consistent with suggestions that this factor identifies individuals with heightened hedonic sensitivity to food.
PALATABILITY AND THE STIMULATION OF APPETITE: A ROLE FOR LEARNING . ; Department of Psychology, University of Sussex
It is well established that the hedonic quality of the flavour of food (ie palatability) is an important determinant of short-term food intake. Detailed analysis of changes in appetite within meals suggested that palatability effects are generated through orosensory reward mechanisms which translate the hedonic evaluation of orosensory stimulation by food into enhanced motivation to eat, indicated by increased hunger in the early stages of meals with palatable foods. However, the hedonic quality of food is in a large part a learned response. Two distinct but interacting types of association may partly underlie the acquisition of palatability. The first, flavour-flavour learning, is based on associations between new flavour elements and existing liked or disliked components such as sweet tastes, while the second, flavour-consequence learning, is based on associations between flavours and post-ingestive effects of nutrients. While many studies have demonstrated that both these associations can increase liking, only recently have we been able to assess whether these acquired likes also stimulate intake. Our recent finding that flavour-nutrient associations can stimulate intake suggest that energy-dense foods may promote active as well as passive over-consumption, while new data also suggest enhanced appetite through flavour-flavour associations. The implications of these observations for understanding overeating in the context of the current obesity crisis is explored.
FLUOXETINE-INDUCED ANOREXIA IS EXAGGERATED IN ADOLESCENT FEMALE RATS THAT EXPERIENCED NEONATAL MATERNAL SEPARATION . ; 1Dental Research Institute, Seoul National University School of Dentistry, 2Department of Biology, The Catholic University of Korea College of Medicine
We have previously reported that repeated maternal separation during pre-weaning period may lead to behavioral depression with alterations in brain 5-HT neurotransmission in rats later in life. In this study, the effects of chronic fluoxetine, a selective 5-HT reuptake inhibitor, on feeding and brain 5-HT system was examined in adolescent female rats that experienced neonatal maternal separation. Sprague-Dawley pups were separated from dam daily for 3h during PND 1 - 14 (MS) or left undisturbed (NH). After weaning on PND 22, 2 or 3 female pups were caged together with ad libitum access to standard chow and water. NH and MS female pups received either an intraperitoneal fluoxetine (5 mg/ 2 ml of saline/ kg) or the same volume of saline daily from PND 35, and food intake and body weight were recorded daily. Between PND 42 and 45, rats were sacrificed by transcardiac perfusion with 4 % PFA for 5-HTT in situ hybridization in the raphe nucleus or by decapitation for HPLC analysis of the brain 5-HT contents. Daily fluoxetine significantly suppressed body weight gains in both NH and MS females with a greater effect in MS group. Chronic fluoxetine tended to reduce the dorsal fat mass of NH females; however, significantly of MS females. Daily food intake was significantly reduced by a single injection of fluoxetine on PND 35 in both groups, and the reduction became bigger in MS group than in NH with repeated fluoxetine. Basal expression level of 5-HTT mRNA in the raphe nucleus of MS group was lower than in NH group. Chronic fluoxetine increased the raphe expression of 5-HTT mRNA in MS female, but not in NH. The results suggest that the increased anorectic property of fluoxetine in MS females may reveal a hyper-responsiveness of the brain 5-HT system by experience of neonatal maternal separation. Tissue contents of 5-HT and its metabolite 5-HIAA in the hypothalamus, hippocampus, pre-frontal cortex, and raphe were analyzed in each experimental group. Supported by KMOST & MOEHRD (JWJ)
ANOSMIA IMPAIRS THE FEEDING RESPONSE TO 2-DEOXY-D-GLUCOSE IN RATS. ; 1Department of Psychology, University of New Orleans, 2Pennington Biomedical Research Center, 3Department of Psychology, Clemson University
In two separate studies, adult female rats with olfactory bulbectomies displayed no increase in food intake during the first 2 hours after an intraperitoneal injection of 350 mg/kg 2-deoxy-D-glucose (2-DG). Behavioral testing demonstrated that the rats with olfactory bulbectomies were anosmic. Rats made anosmic by application of zinc sulfate to the olfactory mucosa also did not display a feeding response to 2-DG. Rats given olfactory bulbectomies also displayed a greatly attenuated feeding response in the first hour after an intraperitoneal injection of 4 U insulin, and displayed a normal drinking response after an intraperitoneal injection of 1 M hypertonic saline. The results with 2-DG can not be attributed to debilitation as the body weights and daily food intakes of rats with olfactory bulbectomies did not differ from control animals at any time during the studies. A previous study found that rats with olfactory bulbectomies did not increase their food intake after dilution of their powder diet with nonnutritive bulk. Other studies have implicated neural pathways mediating taste in the feeding response to 2-DG, and the present results indicate that olfactory pathways are also critically important in the feeding response to 2-DG.
INFLUENCE OF A HIGH FAT DIET ON BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) . ; 1UMR 914 Nutrition Physiology and Ingestive Behavior INRA Agroparistech, 2Laboratoire de Physiologie Neurovégétative, Université Paul Cézanne
BDNF and its high affinity receptor TrkB play a critical role in the synaptic activity and plasticity of mature neurons and enhance adult neurogenesis. Furthermore, treatment with BDNF was found to attenuate weight gain or even cause weight loss and suppress appetite in rats. The aim of this study was to look at the effect of nutrient intake on BDNF concentrations and cellular proliferation in the brain. Adult male Wistar rats were given one of three diets for 6 weeks: high-carbohydrate, high-fat and high-fat pair fed. Rats were sacrificed at the end of the feeding period and BDNF concentrations in the dorsal vagal complex (DVC), hypothalamus and plasma were measured by ELISA on protein extracts of these samples. The cellular proliferation in the DVC was quantified by Ki-67 immunohistochemistry. Neither BDNF levels nor proliferation were modified by the diet. Secondly, using rats that received the same diets, real time PCR was performed in the DVC, hypothalamus and nodose ganglia in order to compare TrkB receptor levels after fasting or refeeding the animals. Results showed significantly lower TrkB levels in the hypothalamus and nodose ganglia of fasted rats given the high fat diet compared to the other dietary groups. These two complementary methodological approaches suggest that there might be a relationship between long-term dietary intake and BDNF but further investigations are needed.
ANOREXIGENIC EFFECTS OF THE BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF) . ; 1UMR 914 Nutrition Physiology and Ingestive Behavior INRA Agroparistech, 2Laboratoire de Physiologie Neurovégétative, Université Paul Cézanne
Treatment with BDNF was found to attenuate weight gain or even cause weight loss in rats. Furthermore, within the dorsal vagal complex, BDNF has been shown to be involved in the control of food intake. Two studies have been conducted (1) to test the electrophysiological response of duodenal vagal afferents to BDNF and (2) to investigate the nature of BDNF-induced food intake depression. In male rats the activation of duodenal vagal afferents in response to BDNF injection (10ng) within the blood supply of the duodenum was recorded ex vivo. Basal vagal afferent neurons’ spontaneous discharge was increased by 156% after BDNF administration. In the second study rats underwent surgery for implantation of a cannula in their fourth ventricle. Food ingestion patterns were recorded every minute for 14 days using an adapted acquisition system. During this period, the animals were treated on specific days with an injection of BDNF (1µg) or an equivalent volume of saline (NaCl 0.9%) via their intra-cerebro-ventricular cannula. BDNF induced a significant decrease in food intake during the 12 hours following injection, but it did not have an effect on the delay in meal onset nor on rate of ingestion and meal frequency. These results indicate that the intake depression is more likely to result from an increased satiety rather than an aversive effect of BDNF. Both studies confirm the hypothesis that peripheral BDNF may act as an anorexigenic factor in the dorsal vagal complex by increasing satiety.
ARCUATE POMC NEURONS SUPPRESS FOOD INTAKE BY DIRECT ACTION ON MC4 RECEPTORS EXPRESSED ON VAGAL AFFERENTS IN THE NTS. ; 1
Meal size can be modulated by brainstem administration of melanocortin receptor-3/4 (MC3/4R) ligands, but the source of endogenous ligands and the mechanism of modulation are not known. Here we show that food intake suppression induced by local activation of arcuate nucleus POMC neurons with leptin in rats is abolished by pretreatment of the caudal brainstem with the MC3/4 antagonist SHU9119 delivered either into the 4th V (e. g. 12-h food intake on day after injection: sal/sal, 13.1 ± 1.2 g; sal/lep (30 pmol), 6.3 ± 0.8 g, p<0.01; SHU (100 pmol)/sal, 14.2 ± 1.0 g, ns; SHU/lep, 11.6 ± 1.3 g, ns) or directly into the NTS. Patch clamp recordings from 140 NTS neurons showed both excitatory and inhibitory effects of α-MSH and its stable analog MTII on frequency but not amplitude of spontaneous and electrical solitary tract stimulation-evoked glutamate currents, consistent with mainly presynaptic modulation. Western blotting revealed presence of MC4 but not MC3-receptor mRNA in rat nodose ganglia. These results are consistent with a role for arcuate-medullary POMC projections in the control of meal size by modulating satiety signaling from the gut through MC4R on central terminals of vagal afferents. In addition, other excitatory inputs to NTS neurons such as projections from the PVH, and vagal motor neurons are likely targets of descending melanocortinergic modulation. Supported by DK47348.