10:00

A Gut (Microbiome) Feeling: Brain Body Interactions Regulating Behaviour Across The Lifespan
John Cryan
University College Cork, Cork, Ireland

The prevalence of brain disorders, including stress-related neuropsychiatric disorders and conditions with cognitive dysfunction, is rising. Poor dietary habits contribute substantially to this accelerating trend. Recently, the communication between the microorganisms within the gastrointestinal tract and the brain along the gut–brain axis has gained prominence as a potential tractable target to modulate brain health. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based interventions for neuropsychiatric disorders. The composition and function of the gut microbiota is robustly influenced by dietary factors to alter gut–brain signalling. To reflect this we recently proposed that a diet–microbiota–gut–brain axis exists that underpins health and well-being.

10:30

From Nutrients To Neurons In The Gourmet Fly: How Brain-Body Interactions Guide Dietary Decisions
Carlos Ribeiro
Champalimaud Foundation, Lisboa, Portugal

A balanced intake of different classes of nutrients is a key determinant of health, wellbeing, and aging. To ensure nutrient homeostasis animals adapt their foraging strategies according to their current and future needs. We want to understand how animals decide what to eat, how these decisions are shaped by brain-body interactions, and how these decisions affect the fitness of the animal. To achieve a mechanistic, integrated, whole-animal understanding of nutritional decision-making we work at the interface of behavior, metabolism, microbiome, and physiology in the adult Drosophila melanogaster. I will discuss how the powerful combination of activity imaging approaches, neurogenetics, connectomics, automated, quantitative behavioral analyses, and nutritional and microbial manipulations is allowing us to achieve a mechanistic understanding of how internal states shape neuronal circuits to optimize complex foraging decisions.

11:00

Food For Thought: Behavioral And Brain Characterization Of Anxiety-To-Eat In Anorexia Nervosa
Kimberly R. Smith
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, United States

Homeostatic and non-homeostatic signals that control ingestive behaviors are often overridden by maladaptive eating behaviors (e.g., food avoidance) to achieve a low body weight in anorexia nervosa (AN). Recently our lab has been interested in characterizing anxiety-to-eat experienced by individuals with AN, with the overarching hypothesis that anxiety-to-eat underlies the severe food avoidance and restrictive eating behaviors that contribute to poor health and treatment outcomes for AN. The present work will focus on our investigations to 1) behaviorally characterize anxiety-to-eat in AN and in healthy individuals, 2) determine the neural correlates of anxiety-to-eat using functional magnetic resonance imaging, 3) identify the neurobiological mechanisms underlying anxiety-to-eat using magnetic resonance spectroscopy, and 4) determine the extent to which anxiety-to-eat improves with behavioral inpatient treatment that includes a meal-based nutritional protocol to achieve rapid weight restoration. Our data suggest that anxiety-to-eat contributes to maladaptive eating behaviors, involves a distributed network of brain regions with a potential therapeutic target, and is treatable with nutritional rehabilitation focused on rapid weight gain and a broadened food repertoire.

11:30

Social Influences On Eating
Suzanne Higgs
School of Psychology, University of Birmingham, Birmingham, United Kingdom

What and how much people eat is influenced by the social context of consumption. For example, people tend to adapt their food choices to those of others, which is known as modelling and they also use their eating behaviours to convey a favourable impression of themselves to other people, which is known as impression management. One particularly striking effect is that people tend to eat more when dining with familiar company compared to eating alone, a phenomenon known as the social facilitation of eating. This presentation will explore recent research on how social factors shape eating behaviours, with a particular focus on social facilitation. I will highlight key gaps in our understanding and suggest promising directions for future research. Gaining deeper insights into the impact of social context on eating choices could lead to new strategies for encouraging healthier eating habits.

12:00

An Influence Of Bmi And High Fat Diet On Food Valuation
Justin Sung¹, Filip Morys¹, Antonietta Canna¹, Xue Davis², Dana M Small^{1, 2}
¹McGIll University, Montreal, QC, Canada, ²Yale University, New Haven, CT, United States

In individuals with healthy weight (HW), implicit versus explicit nutritional signals are relatively more important in determining food value. For example, in auction tasks, willingness to pay (WTP) is positively associated with actual but not estimated energy density and people will pay more for equally pleasant, familiar, priced and caloric foods composed of carbohydrate and fat (COMBO) compared to primarily carbohydrate (CARB) or fat (FAT) alone (Tang 2014; DeFeliceantonio 2018; Perszyk 2021). Unexpectedly, the opposite appears to be true in individuals with overweight or obesity (OW/OB) where WTP is inversely related to actual energy density – an effect mediated by food price (Perszyk 2021). Here, we used an auction task to investigate factors driving WTP in a sample of 51 participants with OW/OB enrolled in a weight loss trial. Consistent with previous findings, a negative association was observed between WTP and actual energy density that was mediated by food price (p=0.02). We also observed an effect of macronutrient in which participants bid more for FAT than CARB (p=0.003), with the magnitude of the effect increasing as BMI increased (p=0.01). Notably, these effects were independent of liking and portion size, which were independent predictors of WTP (p<0.001 and p = 0.02, respectively). Self-reported intake of saturated fat was positively associated with WTP in all macronutrient categories (p=0.007). These results (1) provide further support that price is a greater influence on food choice than is energy density in individuals with OW/OB; (2) reveal a novel association between high fat diet and increased food valuation for all macronutrient categories; and (3) demonstrate a bias for FAT versus CARB foods as a function of increasing BMI.

12:15

Not Only Gut Feelings: Pancreatic Hormone, Amylin, Controls Emotionality And Sociability, In A Sex Divergent Manner.
Suyeun Byun^1,2, Morgan R Sotzen^1,2, Doris I Olekanma^1,2, Mya A Knappenberger^1,2, Karolina P Skibicka^1,2
¹Department of Nutritional Sciences, Pennsylvania State University, State College, PA, United States, ²Huck Institutes of Life Science, Pennsylvania State University, State College, PA, United States

Amylin, a pancreatic peptide hormone, has gained attention for its role in appetite regulation and potential as an anti-obesity treatment; however, its effects on emotionality remain largely unexplored. Given that feeding-related peptides often influence metabolic, but also psychiatric functions, via overlapping neural circuits, we investigated the role of amylin in modulating different aspects of emotionality and sociability: anxiety, depression, aggression, and social behavior. We hypothesized that amylin administration influences emotional behaviors in a sex-specific manner, with the central amygdala (CeA) as a critical site mediating these effects. The CeA was selected as we recently found this nucleus is critical for amylin’s feeding behavior control, and it is a brain site well recognized for its important role in emotionality and sociability control. Male (n=11-14) and female (n=12-19) Sprague-Dawley rats received either systemic (500 μg/kg, IP) or intra-CeA (0.1 or 0.4 μg) amylin. Behavioral assessments included the elevated plus maze (EPM), acoustic startle response (ASR), forced swim test (FST), resident-intruder test (RIT), and social interaction test (SIT), with data analyzed using t-tests or ANOVA with post-hoc Holm-Sidak tests (p<0.05). Systemic and CeA amylin administration induced sex-specific effects on anxiety-like behavior, with anxiolytic responses in males and anxiogenic responses in females. Intra-CeA amylin increased depressive-like behavior in females but had no effect in males. Aggressive behavior was reduced in both sexes, while systemic, but not intra-CeA, amylin increased social interaction. These findings suggest that amylin modulates emotional and social behaviors in a sex-dependent manner, with the CeA as a key neural substrate. Considering previous anti-obesity therapeutics have been withdrawn from the market because of emotionality side effects, our results highlight the importance of understanding these effects in both sexes for the development of safe amylin-based obesity treatments that minimize psychiatric risks.

12:30

Stress Engages The Noradrenergic Brainstem-To-Hypothalamus Circuit To Suppress Appetite.
Myungmo An^1,2, Junkoo Park^1,2, Sumin Lee^3,4, Se-Young Choi^3,4, Sung-Yon Kim^1,2
¹Institute of molecular biology and genetics, Seoul, South Korea, ²Department of chemistry Seoul National University, Seoul, South Korea, ³Department of physiology and neuroscience Seoul National University, Seoul, South Korea, ⁴Dental research institute, Seoul, South Korea

Stress triggers adaptive behavioral shifts that override homeostatic drives such as appetite, yet the underlying neural mechanisms remain poorly understood. Here, we identify a noradrenergic brainstem-to-hypothalamus circuit that mediates stress-induced appetite suppression in mice. Using in vivo fiber photometry, we found that noradrenergic locus coeruleus (LC^NA) neurons exhibit persistent activity extending beyond acute restraint stress, temporally aligned with feeding suppression (n=7). Inhibition of LC^NA neurons (n=11) or their projections to the paraventricular hypothalamus (PVH) (n=19) prevents stress-induced appetite suppression, whereas optogenetic activation of LC^NA neurons mimics stress effects that suppress feeding (n=7). Real-time norepinephrine recordings in the PVH show sustained elevation after restraint stress, correlating with the duration of feeding suppression (n=8). Pharmacological blockade of α1-adrenergic receptors in the PVH, particularly the α1b subtype, abolishes stress-induced appetite suppression (n=9). Notably, this circuit is also required for feeding suppression after chronic stress (n=5). Collectively, our findings pinpoint the LC^NA-PVH^α1b noradrenergic circuit as a key driver of sustained appetite suppression following stress, uncovering a direct link between brain stem arousal center and hypothalamic feeding circuits.

12:45

The Role Of The Basolateral Amygdala And The Lateral Hypothalamus In Social Stress-Induced Appetitive Motivation
Megan L. Mcgraw, Cooper C. Christensen, Ai-Jun Li, Emily Qualls-Creekmore
Washington State University, Pullman, WA, United States

Stress profoundly influences appetitive motivation. While stress can promote maladaptive behaviors such as behavioral addictions or contribute to disorders like depression, the underlying neural mechanisms remain unclear. The basolateral amygdala (BLA) and lateral hypothalamus (LH) are key regulators of both stress and motivated behaviors, yet their direct interactions remain underexplored, particularly across sexes. Our recent findings reveal that chronic non-discriminatory social defeat stress (CNSDS) elicits opposite effects on appetitive behavior in male and female mice. We hypothesize that BLA glutamatergic projections to the LH (BLA^Glut→LH) mediate these sex-specific effects. To test this hypothesis, we measured neural activity in response to CNSDS and tested the effect of circuit manipulation on appetitive motivated behavior. All experiments were conducted in male and female C57BL/6J or Vglut2-ires-cre mice, n = 5-7 per group. First, we confirmed direct monosynaptic BLA^Glut→LH connectivity using cell-type specific viral tracing. Next, we found that cFos expression after CNSDS was increased in the BLA and LH of both sexes. Fiber photometry also revealed that calcium dynamics in BLA^Glut terminals in the LH are increased during CNSDS in both sexes. Finally, optogenetic excitation of the BLA^Glut→LH circuit enhances motivated behavior in non-stressed mice of both sexes. Given the established sex differences in BLA physiology, and heterogenous molecular and functional profile of BLA neurons, we propose that CNSDS engages different BLA subpopulations in males and females that translate into opposing outcomes on motivation. These findings highlight the need for sex-inclusive neurobiological research and may inform targeted interventions for stress-related disorders.

1:00

Functional Neuroimaging Of Impulsivity, Negative Emotional Reactivity And Monetary Reward Processing In Adults With Obesity And Binge Eating Symptoms
Alisa Musatova¹, Navpreet Chhina¹, Rioghnach Hannan¹, Eleanor Brian¹, Moaz Al Lababidi¹, Ghadah Aldubaikhi¹, Isabelle Franco¹, Madhawi Aldhwayan², Werd Al-Najim³, Aruchuna Ruban⁴, Michael A Glaysher⁵, Christina G Prechtl⁶, James P Byrne⁵, Julian P Teare⁴, Anthony P Goldstone¹
¹PsychoNeuroEndocrinology Research Group, Division of Psychiatry, Department of Brain Sciences, Imperial College London, London, United Kingdom, ²Community Health Sciences Department, King Saud University, Riyadh, Saudi Arabia, ³Department of Metabolism, Diabetes and Reproduction, Imperial College London, London, United Kingdom, ⁴Department of Surgery and Cancer, Imperial College London, London, United Kingdom, ⁵Division of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, ⁶Clinical Trials Unit, Department of Public Health, Imperial College London, London, United Kingdom

Introduction: Binge eating symptoms (BES) may be associated with impulsivity and emotional regulation difficulties (risk factors for disordered eating, with binge episodes often precipitated by stress) and abnormal reward processing. The neural correlates of these facets in BES are uncertain. Methods: N=96 adults with obesity ± type 2 diabetes mellitus with (≥ 1 episode/mo) or without BES (BMI/sex-matched) completed questionnaires, and n=44 non-food Go/No-Go (GNG), negative emotional reactivity (NERT), monetary incentive delay (MID) fMRI tasks after an overnight fast. ROI/whole-brain analyses examined BOLD signal during successful motor response inhibition (GNG), unpleasant (vs. neutral) image viewing (NERT), win/loss vs. neutral trial anticipation (MID) ± plasma glucose/BMI as covariates. Results: In BES vs. non-BES there was: (i) in GNG task, more commission errors, and during successful No-Go trials lower BOLD signal in precentral gyrus (pCG), operculum, posterior cingulate gyrus, precuneus, lat. occipital cortex, higher BOLD signal in mid./sup. frontal gyrus, pCG; (ii) higher trait impulsivity from negative/positive urgency (UPPS-P), but not monetary temporal impulsivity (delay discounting), (iii) worse mood (HADS, BDI-II), quality-of-life (IWQoL-Lite, SF36); (iv) in NERT, lower BOLD signal to unpleasant images in amygdala (negatively correlating with impaired QoL), subcallosal cortex, lingual gyrus; (v) similar BOLD signal during monetary reward anticipation. Conclusion: Monetary reward processing was unaffected by BES. Heightened urgency and impaired motor response inhibition are consistent with greater impulsivity in BES. Attenuated negative emotional reactivity in amygdala and subcallosal cortex in BES may indicate habituation to chronic stress.

1:15

Gip Receptor Agonism Modulates Aversive Behaviors And Parabrachial Cgrp Neuron Activity (New Investigator Travel Awardee)
Haley Province¹, Nathan Leong¹, Jessica Xia¹, Nikolas Hayes¹, Lisa Beutler¹
¹Northwestern University, Department of Medicine (Endocrinology), Chicago, IL, United States, ²Northwestern University, Department of Medicine (Endocrinology), Chicago, IL, United States, ³Northwestern University, Department of Medicine (Endocrinology), Chicago, IL, United States, ⁴Northwestern University, Department of Medicine (Endocrinology), Chicago, IL, United States, ⁵Northwestern University, Department of Medicine (Endocrinology), Chicago, IL, United States

Glucose-dependent insulinotropic polypeptide (GIP) is a gut-derived incretin hormone that acts on GIP receptors (GIPR) distributed across the central nervous system to regulate energy homeostasis. Pharmacologic activation of the GIPR modestly suppresses feeding, and the recently developed obesity and diabetes therapy tirzepatide acts in part as a GIPR agonist. Recent reports have also demonstrated that central GIP receptor agonism may also be anti-aversive. Data from multiple species have shown that GIPR agonism markedly attenuates nausea and vomiting in response to a variety of unpleasant stimuli. However, the mechanism by which GIP signaling mediates anti-aversive effects during inflammation is not fully understood. The inflammatory cytokine interleukin-1β (IL-1β) is elevated in many inflammatory diseases and its ability to induce aversion is well-known. Here, we show that the GIPR agonist D-Ala2-GIP abrogates IL-1β-induced taste aversion without reducing its anorexigenic effects in mice. To study the neural substrates underlying this phenomenon, we looked at neuronal activity of a well-defined aversive node: calcitonin-gene related peptide-expressing neurons in the parabrachial nucleus (CGRP neurons). Our in vivo fiber photometry data demonstrate that IL-1β increases CGRP neural activity, and that this is significantly attenuated by co-administration of D-Ala2-GIP. Taken together, these data suggest that the aversive effects of IL-1β are at least partially mediated by CGRP neurons and that GIPR agonism blunts the aversive effects of IL-1β via these neurons. Moreover, our data supports recent studies that anorexia and aversion are regulated by distinct neural pathways.

12:00

Oro-Sensory And Post-Ingestive Dopamine Signals Interact To Control Food Reward(New Investigator Travel Awardee)
Tung T. Bui¹, Alec E. Hartle¹, Bhaskar Ray², Michael Galligan¹, Zachary Moore¹, Srijan Sengupta², Alexandra DiFeliceantonio³, William M. Howe¹
¹School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States, ²Department of Statistics, North Carolina State University, Raleigh, NC, United States, ³Department of Human Nutrition, Foods, and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States

The oro-sensory and post-ingestive signals generated by a food independently contribute to its rewarding qualities, in part through their effects on release of dopamine (DA) in the striatum. DA release evoked by these individual components of food intake emerges over radically different timescales, though interestingly, emerging evidence suggests that the magnitude of release associated with these signals is correlated. Here, we designed a set of studies to test the hypothesis that taste and post-ingestive DA signals causally interact to determine food reward. First, mice (n=7) were allowed to freely consume any of three different food stimuli presented in tandem (sugar, fat, or a combination of the two) as DA release was recorded in the dorsal striatum (DS) with fiber photometry. Here, DA release roughly tracked expressed food preference, with the largest changes in DA observed as mice consumed their most preferred food type. Next, a separate cohort of mice (n=7) was prepared with intragastric catheters, and DA release was recorded as mice received intragastric infusions of each macronutrient combination above. These experiments revealed a window of time 10-20 minutes post infusion where DA release was significantly altered by nutrients reaching the stomach. Using optogenetics, we found that stimulating DA cell bodies at this timepoint (10-20 minutes following consumption) selectively amplified intake of that food in the future by approximately 5 folds (DAT-Cre mice; n=7 ChR2, n=5 EYFP control). This effect on intake was mirrored by an increase in DA release during consumption of that food. Our combined data suggest that post-ingestive DA signals causally influence DA released in response to future oro-sensory stimulation, and this interaction is key for food reward.

12:15

High Or Low Dietary Sweet Taste Exposure Do Not Affect Sweet Taste Liking Or Body Weight
Eva Cad¹, Monica Mars¹, Leone Pretorius², Claudia Tang², Merel van der Kruijssen¹, Hanne de Jong¹, Michiel Balvers¹, Katherine Appleton², Kees de Graaf¹
¹Wageningen University and Research, Wageningen, Netherlands, ²Bournemouth Univrersity, Bournemouth, United Kingdom

Rationale: Humans love sweet taste, but our innate liking may result in excessive consumption, high energy intake and overweight. Authoritative public health agencies follow the reasoning: more frequent exposure to sweet taste increases preferences for sweetness, which leads to greater sugar and calorie intake and, eventually, leads to higher body weight. However, none of these steps have been confirmed with experimental data. Hypothesis: There will be no effects of high or low dietary sweet taste exposure on sweet taste liking, energy intake or body weight. Species: Human adults Number of subjects: 180 Procedures: A large-scale 6-month, randomized clinical trial (registration: clinicaltrials.gov NCT04497974: Sweet Tooth: Nature or Nurture?) was undertaken with three experimental groups: higher, regular and lower dietary sweetness exposure. Ad-libitum diets with partial food provision were designed as equicaloric. Outcomes were sweet taste liking, sweet taste perception, energy intake, body weight and several biomarkers for diabetes and cardiovascular disease. Results: A higher/lower dietary exposure to sweet taste did not lead to higher/lower sweet taste liking, changes in perception, energy intakes, body weight or biomarkers for diabetes and cardiovascular disease. Subjects also spontaneously returned to baseline levels of sweet food intake at 1 and 4 months follow up. Conclusions: Our findings directly contradict the assumptions made by many public health agencies, and suggest that, while overweight remains a global public health concern, excess energy intake is unlikely to be affected by advice to reduce our exposure to, or intakes of, sweet taste. Dietary recommendations to avoid energy overconsumption should instead focus on effective evidence-based strategies.

12:30

Olfactory Bulb Glp-1 System Influences Sensory Perception Of Food And Feeding Behaviour
Mireia Montaner¹, Jo E Lewis¹, Jessica Denom², Christophe Magnan², Hirac Gurden², Fiona Gribble¹, Frank Reimann¹
¹Institute of Metabolic Science & MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, UK., Cambridge, United Kingdom, ²Universite Paris Cite, Unit of Functional and Adaptive Biology (BFA), UMR 8251 CNRS, F-75013, Paris, France., Paris, France

The olfactory bulb (OB) is the sensory structure that processes food odours and plays a fundamental role in the appreciation of food palatability. Within the OB, glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) is expressed in the main output neurons (OB^GLP-1R). Moreover, a specific population of OB interneurons has been identified as GLP-1-producing preproglucagon (OB^PPG) cells. Several studies support the existence of a functional and physiologically relevant GLP-1 system within the OB. However, how food odours influence OB^GLP-1Rdriven neurocircuits and how these circuits modulate feeding behaviour is unknown. To investigate the proposed relationship between OB GLP-1 and food odours, and assess its effects on feeding behaviour, we combined a standard olfactory behavioural approach with pharmacological manipulation, chemogenetics and in vivo Ca²⁺imaging. Experiments were conducted on lean and diet-induced obese mice. During fiber photometry recordings, the presentation of food odours triggered a rapid increase in Ca²⁺ levels in OB^PPG neurons of lean mice. Gq-DREADD activation of OB^PPGneurons in lean mice reduced the latency to locate a hidden chocolate pellet underneath a layer of bedding, suggesting enhanced olfactory-guided behaviour. Subsequent consumption of the pellet was decreased. Similarly, a local OB injection of the GLP-1R agonist Ex-4 in obese mice also reduced the latency to find the hidden chocolate. Furthermore, activation of Gq-DREADDs in OB^GLP-1Rcells during refeeding tests led to a reduction in both chow and high-fat diet intake in obese mice. These findings suggest a role for GLP-1/GLP-1R in the OB in sensory detection of food and feeding behaviour, highlighting the influence of specificOB^GLP-1R-driven neurocircuits in food perception and consumption.

12:45

Olfaction And Feeding Behaviour: NEuronal Substrates Underlying Odour Modulation Of Neuronal Circuits Regulating Food Intake
Louise Eygret¹, Morgane Martin¹, Alexandra Sere¹, Farha Bouteldja¹, Vincent Simon², Daniela Cota², Xavier Fioramonti¹, David Jarriault¹
¹NutriNeuro (INRAE UMR 1286), Bordeaux, France, ²Neurocentre Magendie, Bordeaux, France

Maintaining a stable body weight is a challenge for a growing part of the population, and current pharmacological treatments can come with side effects. The olfactory system plays a key role in nutrition and could offer a non-invasive alternative for regulating eating behaviour. Food intake is mainly controlled by hypothalamic AgRP (orexigenic) and POMC (anorexigenic) neurons, which can rapidly respond to food cues before consumption, suggesting a sensory influence. We hypothesize that appetitive odorant molecules modulate the activity of hypothalamic neurons, providing an olfactory-driven mechanism regulating food intake. We identified bacon and peanut butter as attractive odorants for male and female mice based on investigation times. These odorant molecules revealed a potent appetitive effect in automated food intake monitoring experiments. Patch-clamp electrophysiological recordings from brain slices of mice exposed to these odorants during 30 min showed that they induced decreased firing in POMC neurons. No effect was observed on AgRP neuron activity. In vivo fiber photometry showed a modulation of POMC and AgRP neuron activity during active sniffing of the attractive odorants. These odorants induced an instant decrease in AgRP neuron activity and an increased activity in POMC neurons. Our results suggest that attractive food-related odours modify the electrical activity of neurons within the melanocortin network, emphasizing the sensory modulation of hypothalamic feeding regulation. Future work will map the involved projections between the olfactory system and the hypothalamus. Understanding how olfactory cues influence hypothalamic circuits will be useful for developing safer, innovative therapies for energy balance disorders.

1:00

Glp-1 Receptor Agonists Significantly Impair Taste Function
Richard Doty¹, Rafa Khan¹
¹University of Pennsylvania, Philadelphia, PA 19104, PA, United States, ²University of Pennsylvania, Philadelphia, PA 19104, PA, United States

Over 10% of the US population are prescribed glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to combat obesity. Although they decrease cravings for foods, their influence on chemosensory function is unknown. We employed state-of-the-art quantitative taste and smell tests to address this issue. The 53-item Waterless Empirical Taste Test (WETT®) and the 40-item University of Pennsylvania Smell Identification Test (UPSIT®) were completed by 46 persons taking GLP-1 RAs and 46 controls matched on age, sex, smoking behavior, and COVID-19 infection histories. Data were analyzed using analyses of variance. The WETT® scores were significantly diminished in the GLP-1 RA group relative to controls [total means (95% CIs) = 28.61 (25.66,31.56) and 40.63 (38.35,42.91), p <0.001, η2 = 0.37]. Eighty five percent of the GLP-1 subjects scored worse than their individually matched controls. All 5 WETT® subtest scores were similarly affected (ps <0.001). Smell function, although slightly decreased on average, was not significantly impacted (p = 0.076). Women outperformed men on all tests. Remarkably, UPSIT® and WETT® scores were higher, i.e., better, in those reporting nausea, diarrhoea, and other GLP-1-related side effects. This study demonstrates, for the first time, that GLP-1 RAs alter the function of a major sensory system, significantly depressing the perception of all five basic taste qualities. The physiologic basis of this effect is unknown but may involve GLP-1 receptors in the brainstem and afferent taste pathways, as well as vagus nerve-related processes

1:15

Agrp Neurons Distinguish Oral Sugars From Sweeteners
Misgana Y Ghidewon^1.2, Laryssa O Coutinho², Milena S Almeida^2,, Sevinch Rakhmonova², Alisha A Acosta², Amber L Alhadeff^1,2
¹University of Pennsylvania, Philadelphia, PA, United States, ²Monell Chemical Senses Center, Philadelphia, PA, United States

Food intake requires intricate coordination between orosensory signaling and central feeding circuits that initiate and maintain feeding. Yet, the impact of oral sugar sensing on homeostatic feeding circuits is not fully understood. Here, we combined intraoral cannulation with in vivo fiber photometry in mice to understand how isolated taste cues influence hypothalamic agouti-related protein (AgRP)-expressing neuron activity. Small volumes of intraorally delivered nutrients (Ensure) robustly and transiently inhibited AgRP neuron activity (n=5, paired t-test, p<0.05). We next determined that oral glucose (sugar), but not saccharin (non-caloric sweet taste) inhibits AgRP neuron activity (n=14, 2-way ANOVA, p<0.0001). This is independent of post-ingestive signaling (n=9, paired t-test, p=ns). Furthermore, food-predicting (umami and salty) and avoided (sour and bitter) taste stimuli did not impact AgRP neuron activity (n=18, 2-way ANOVA, p=ns). This suggests that taste alone is not a salient modulator of AgRP neuron activity. Instead, sugars and sweeteners may utilize different mechanisms to modulate AgRP neuron activity. To test this hypothesis, we first reanalyzed publicly available single-cell datasets and confirmed that sodium glucose cotransporter 1 (SGLT1), which transports glucose but not saccharin, is expressed in taste receptor-expressing cells within the fungiform papillae. We then pharmacologically blocked SGLT1 and showed that this eliminated the effects of intraoral glucose on AgRP neuron activity (n=12, 2-way ANOVA, p<0.0001). Overall, these findings provide evidence that caloric sugar and non-caloric sweeteners are distinguished in the mouth and transmitted to AgRP neurons, a feat that has typically been ascribed only to post-ingestive signaling.

3:00

Might Energy Expenditure And Physical Exercise Be Implicated In The Control Of Appetite In Adolescents With Obesity?
David Thivel
AME2P Laboratory, CLERMONT-FERRAND, France

Long considered as two independent sides and levers of our energy balance, physical activity and energy intake keep dialoging and interacting, impacting the control of our overall energy homeostasis and health. The present talk will try to propose an overview of the effect of physical exercise, energy expenditure and energy metabolism on appetite control, energy intake and food reward in adolescents with obesity. The behavioral but also physiological, neuro-physiological and cognitive pathways involved will be discussed and new results regarding the implication of our energy metabolism and substrate use will be presented.

3:30

To Run Or Not To Run That Is The Question
Kevin W Williams
Center for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States

Regular physical activity has profound effects on brain function, influencing cognition, mood, energy balance, and glucose metabolism. Recent studies highlight that exercise induces structural and functional changes in key metabolic circuits. These dynamic neural adaptations are associated with enhanced insulin sensitivity, appetite regulation, and improved systemic metabolism. While the precise mechanisms linking physical activity to brain-mediated metabolic benefits remain under investigation, emerging evidence suggests that key brain regions, including the hypothalamus, play a critical role in these adaptations. Understanding how exercise modulates neural activity and plasticity will provide insights into its therapeutic potential for metabolic and neurological disorders. In this presentation, I will discuss recent advances in our understanding of exercise-induced neuroplasticity, with a particular focus on hypothalamic circuits that regulate energy balance and glucose metabolism. I will highlight how exercise engages metabolically relevant neuron populations and explore how these changes contribute to improvements in metabolic health.

4:00

Regular Intense Activity Is Associated With Lower Sweet Taste Sensitivity And Increased Sugar Intake
Isabella Kimmeswenger^1,2, Marlies Gaider^2,3,4, Kevin Doppelmayer¹, Jakob Ley⁵, Barbara Lieder^1,3,4
¹Institute of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria, ²2 Vienna Doctoral School in Chemistry (DoSChem), University of Vienna, Vienna, Austria, ³Christian Doppler Laboratory for Taste Research, Faculty of Chemistry, University of Vienna, Vienna, Austria, ⁴Institute of Clinical Nutrition, University of Hohenheim, Stuttgart, Germany, ⁵Symrise AG, Holzminden, Germany

Taste sensitivity may affect food choices. In obese individuals, micro-inflammation is suspected to reduce taste sensitivity. Since intense physical activity is also associated with increased inflammatory markers, we hypothesize that higher cytokine levels in persons that perform regular intense exercise affects the taste apparatus and consequently sweet taste sensitivity and food choices. Data concerning salivary IL-6 and urinary 8-iso-PGF2-a concentrations, body composition, sweet taste sensitivity and preferences, dietary intake of sweet food, physical activity, size and area of fungiform papillae was collected from participants (m/f) who exercise ≥6 hours per week (n=34) or ≤2.5 hours per week (n=31). Data was analyzed using PCA followed by linear regression models, Student’s t-tests or Mann-Whitney-U test. Overall, 44% of cumulative proportion of variance was explained by two principal components: variables related to body composition and morphological aspects of fungiform papillae were summarized in PC1, while sweet taste sensitivity, consumption of sweet foods and salivary IL-6 concentration contributed mainly to PC2. Group comparisons for the variables demonstrated that the active group had on average higher salivary IL-6 concentrations and a decreased sweet taste sensitivity, accompanied by a higher consumption of sweet foods. In addition, the active participants had 25±5% less fungiform papillae compared to less active participants. In conclusion, the results support the hypothesis that regular intense physical activity affects the taste apparatus, possibly via increased cytokine levels. The reduced sweet taste sensitivity in highly active persons may facilitate an increased sugar intake, assisting the supply of elevated energy needs for carbohydrates

3:00

Measurement Of The Reinforcing Value Of Food In Infancy
Amanda K Crandall¹, Ashley N. Gearhardt², Alison L. Miller³, Katherine L. Rosenblum⁴, Julie C. Lumeng¹
¹Departments of Pediatrics University of Michigan Medical School, Ann Arbor, MI, United States, ²Department of Psychology, University of Michigan College of Literature, Science, and the Arts, Ann Arbor, MI, United States, ³Department of Health Behavior & Health Equity, University of Michigan School of Public Health, Ann Arbor, MI, United States, ⁴Departments of Psychiatry and Obstetrics & Gynecology, University of Michigan Medical School, Ann Arbor, MI, United States

The reinforcing value (RRV) of food is thought to have genetic origins and emerge during infancy. Using a standardized task, the current study examined the developmental progression of the RRV of food from 9 to 12 months. 175 infants were offered, in counterbalanced order, the opportunity to press a lever for food and a block to play with. The presses required to win the reinforcer progressed by 2 after each round. The mother completed surveys on the child’s appetite that were appropriate for the age point. Regression analyses controlling for order of presentation revealed that RRV, operationalized as the number of presses for the highest schedule completed, for food and nonfood reinforcers were positively associated with one another within (9m, β=0.40, p<.001; 12m, β=0.49, p<.001), but not across timepoints (p>.05). The RRV of food was associated with both weight for length z-score (β=0.18, p=.011) and conditional weight gain (β=0.09, p=0.033) at 12, but not 9 months. Likewise, the proportion of presses for food was associated with the child’s score on the CEBQ enjoyment of food (β=0.56, p=.020) and satiety responsiveness (β=-0.85, p=.002) scales at 12 months. Counterintuitively, RRV at 9 months was associated with lower general appetite scores on the BEBQ (β=-0.22, p=.016). These findings suggest that although a 9-month-old infant may respond to an RRV task, their responses do not equate to the eating behavior or growth in the way they do among older infants, children, and adults. This pattern emerges closer to 12 months, perhaps because the infant is moving into a developmental phase marked by a much greater proportion of their caloric intake from the solid foods used in the task.

3:15

&Ldquo;Cookies Make Me Feel Like Life Is Good&Rdquo;: Food-Related Emotional Expectancies In Children And Adolescents
Jenna R. Cummings¹, Maddy Roberts¹, Ashlin James¹, Mabel S.F. Kouk¹, Aimee E. Pink², Julia M.P. Bittner³, Albert Lee⁴, Bobby Cheon³, Leah M. Lipsky³, Tonja R. Nansel³
¹University of Liverpool, Liverpool, United Kingdom, ²Agency for Science, Technology and Research (A*STAR), Singapore, Singapore, ³Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, United States, ⁴Nanyang Technological University, Singapore, Singapore

Rationale. Modifying influences on eating behaviours early in life could prevent disease. Food-related emotional expectancies are predictions about how foods affect emotions. In adults, positive discretionary-food expectancies (e.g., “I expect to feel happy while eating pizza”) drive intake of less healthful foods and are modifiable; however, this is unexamined in young people. We investigated food-related emotional expectancies in children (6 years) and adolescents (14-17 years). Hypothesis. Positive discretionary-food expectancies would predict less healthful food choices. Given that core-food expectancies (e.g., “I expect to feel happy while eating apples”) are unrelated to eating behaviours in adults, we had no hypothesis about those expectancies. Participants. 78 children and 1248 adolescents. Procedures. Children completed (1) free-word association, saying their first thoughts in response to food prompts, (2) the Anticipated Effects of Food Scale (AEFS) for Children, and (3) eating a meal and snacks under observation. Adolescents (1) answered the AEFS for Adolescents and (2) chose between foods varying in healthfulness online. Results. Even 6-year-old children held strong food-related emotional expectancies (e.g., “Cookies make me feel like life is good,” “Bananas make me feel weird”). Positive discretionary-food expectancies were associated with less healthful food choices in children and adolescents (medium effect sizes). Positive core-food expectancies were associated with more healthful food choices (medium effect sizes). Conclusions. Positive discretionary-food expectancies may reinforce unhealthful food choices across the lifespan, while positive core-food expectancies may promote health specifically in young people.

3:30

Working Memory Moderates The Relationship Between Attentional Bias And Eating Behavior
Jessica H. Liu¹, Afroditi Papantoni², Kyle S. Burger²
¹The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, ²Monell Chemical Senses Center, Philadelphia, PA, United States

Impaired working memory (WM) and attentional bias towards food have independently been associated with aberrant eating behavior patterns and elevated weight. Here, we hypothesize lower WM and higher attentional bias would be related to faster energy eating rates, increased kcal intake, and higher body mass. In this cross-sectional study, a 2-step nback (WM) and a food ad eye-tracking paradigm (time to first fixation bias on food, TTFF; total ad duration bias) were assessed in children (n=38; F=17; age=8±1.65). The eye-tracking paradigm was presented as a YouTube video with pop-up ads depicting food and toy pictures. Food intake (total kcals) and energy eating rate (kcals/min) were assessed via an ad lib taste test of 6 ultra-processed snacks, e.g., Oreos. Adjusting for confounds, ANOVAs were used to test for WM*attentional bias interactions with significance set to p<0.05. WM moderated the relation between TTFF and kcals consumed, where lower WM and faster TTFF were related to higher kcal consumption (p=0.057). We also observed faster TTFF was related to increased eating rate (p=0.06). No significant interactions or main effects were seen with ad duration bias (p>0.05). This suggests that implicit attentional bias (vs. sustained attentional bias) for foods plays a larger role in influencing ingestive behavior, possibly through largely unconscious processes. Further, those with poorer WM may be more susceptible to food cue-potentiated overconsumption. Further research is needed to understand the role of WM and attentional bias on food and eating behavior. Future healthy eating interventions, such as cue-reappraisal approaches, should consider individual differences in WM to tailor their intervention.

3:45

Using Machine Learning To Identify Task Fmri Predictors Of Appetite Ratings And Weight Status In Adolescents
Trinity Cheng¹, Liuyi Chen¹, Afroditi Papantoni², Susan Carnell¹
¹Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Monell Chemical Senses Center, Philadelphia, PA, United States

Food cue responsiveness is thought to influence body weight. Task fMRI studies have identified brain regions activated by exposure to food cues. However, the degree to which responding within these regions is capable of predicting subjective appetite and body weight is unclear. We applied machine learning models to fMRI food cue reactivity task data from 77 adolescents (16.3±1.27y; 37M 40F; BMIz=0.64±1.21) to test whether BOLD responses to high energy-density [ED] food vs. non-food images could classify participants into groups based on subjective appetite ratings in response to high-ED foods (top 25% vs. bottom 75% on wanting (assessed during scan) and liking (assessed outside scanner)), and weight (overweight/obesity [OV/OB] vs. healthy-weight). To identify regions of interest [ROIs] we used NeuroQuery, an online meta-analysis tool based on 13,459 neuroimaging studies, to create statistical maps of activation associated with six terms: appetite, eating, diet, food, hunger, obesity. Peak cluster coordinates (z-score>3) were identified within all six maps and used to assemble a set of 45 6-mm spherical ROIs. Mean beta values representing BOLD responses to high-ED vs. non-food images were extracted from each ROI. A supervised Random Forest algorithm with 5-fold cross-validation showed limited performance in classifying top 25% wanting (57.14% accuracy, 61.88% AUC), top 25% liking (75.32% accuracy, 57.53% AUC), and OW/OB status (59.74% accuracy, 64.43% AUC). These preliminary models suggest low power of BOLD responses within our selected ROIs to predict subjective appetite and weight in our sample. Future work will consider alternative feature selection methods and whole brain connectivity approaches in larger samples with more variance in weight/eating phenotypes.

4:00

Maternal Prebiotic Supplementation Improves Vagal Function And Diet Induced Obesity In Offspring
Jennifer M. Houston¹, Jillian M. Allen², Rachel E. Lippincott², Eden E. Crain², Jung H. Byun², Dulce M. Minaya², Kellie L. Tamashiro³, Claire B. de La Serre¹
¹Colorado State University, Fort Collins, CO, United States, ²University of Georgia, Athens, GA, United States, ³Johns Hopkins University, Baltimore, MD, United States

Maternal obesity increases risk for metabolic disorders in offspring. Gut-innervating vagal afferents terminate in the nucleus of the solitary tract (NTS), conveying post-ingestive cues to regulate meal size. Rat pups born to high fat (HF) diet-fed dams show reduced sensitivity to gut satiety peptides and post-prandial NTS activation linked to altered feeding. A HF-type gut microbiota is necessary and sufficient to alter vagal structure and function. We hypothesized that improving microbiota composition in HF-fed dams will enhance offspring gut-brain communication. Sprague-Dawley dams were fed a chow (LF), HF, or high fat supplemented with prebiotics (resistant starch, RS, HF+12% RS) diet during pregnancy and lactation. Offspring were weaned onto a LF diet. By post-natal day 14 (P14), HF offspring were heavier than HFRS (p<0.05) and LF (p<0.05) pups. Immunostaining of NTS at P21 showed a decrease in vagal innervation in HF pups compared to LF and HFRS offspring. This was inverted in adulthood but did not improve function, as HF offspring failed to reduce food intake in response to gut satiety peptide cholecystokinin (CCK, 1.5ug/ml/kg). This was rescued in HFRS pups, associated with a reduction in meal size and indicating improved vagal function. When challenged with a HF diet, HF pups gained significantly more weight than HFRS offspring (p<0.05), highlighting protective effects of maternal supplementation. This may be limited to gut-originating signals as both HF and HFRS offspring displayed a deficit in NTS leptin signaling compared to LF pups. We concluded that maternal HF diet alters vagal communication in offspring, increasing risk for diet-induced obesity. Some effects appear to be microbiota driven and improved with maternal RS supplementation.

4:15

Effects Of Semaglutide Injections On Weight And Body Composition In An Adolescent Rodent Model.
Austin M. Mills, CJ Petty, Emily E. Noble
University of Georgia, Athens, GA, United States

Glucagon like peptide receptor (GLP-1R) agonists are key players for treating obesity, and some are FDA approved for use in adolescents as young as twelve; however, the long-term developmental effects are unknown. We investigated the effects of the GLP-1R agonist semaglutide (sema) in a rodent model of adolescent obesogenic diet consumption and hypothesized that sema would reduce weight gain and growth. Male and female adolescent Sprague Dawley rats (PND 28) were fed a high fat, high sugar diet alternating between 60% kcal from fat and 45% kcal from fat as well as an 11% high fructose corn syrup solution where flavored and unflavored drinks were offered on different days (HFHS; n=8/sex). Rats on the control diet (CD; n=8/sex) were fed standard chow with two bottles of water. Data were analyzed using 3-way ANOVAs for body weight and 2-way ANOVAs for body composition, or t tests for body composition between diet groups; α<0.05 was considered statistically significant. Compared with CD, there was a significant increase in body fat percentage in both male and female HFHS-fed rats within one week. Rats were sub-divided to receive daily injections of sema (70 µg/ml) or vehicle (n=4/group per sex). Female rats treated with sema showed reduced weight gain driven by reductions in body fat in diet both groups. In contrast, sema-treated male rats showed reduced weight gain due to reduced lean mass and length growth. These studies elucidate a sex difference in adolescent responses to sema, which may be due to the timing of puberty relative to introduction of sema (a topic of ongoing investigation). Given that sema is already in widespread use, these findings have important clinical implications.

10:00

Effects Of Semaglutide On Wheel Running And Associated Dopamine Dynamics In Mice
E.P. Foscue¹, R. TRINKO¹, E. KONG¹, J. LARA JIMENEZ¹, K. STANKEWICH¹, S.L. THOMPSON¹, A. CORSTENS¹, M.J. SERLIE⁴, J.R. TAYLOR^1,2,3, R.J. DILEONE^1,2,3
¹Department of Psychiatry, Yale University, New Haven, CT, United States, ²Department of Neuroscience, Yale University, New Haven, CT, United States, ³Wu-Tsai Institute, Yale University, New Haven, CT, United States, ⁴Department of Endocrinology, Yale University, New Haven, CT, United States

Glucagon-like peptide-1 (GLP-1) receptor agonists are effective anti-obesity agents that act via reduction in food intake. There is also evidence for drug and alcohol intake with less known about non-ingestive behavioral outcomes. We examined the effects of the long-acting GLP-1 receptor agonist semaglutide on voluntary wheel running and motivation to run in mice. In both lean and diet-induced obese (DIO) mice, semaglutide suppressed voluntary running behavior, independent of weight loss or caloric restriction. To directly assess motivation to run, we employed a progressive ratio operant task in which mice nose-poked to gain wheel access; semaglutide significantly reduced operant responding in both dietary conditions. No differences in semaglutide effects were observed between lean and DIO mice, and males and females both showed similar responses. Running bout analysis demonstrated that semaglutide causes a reduction in running bout length with no changes in bout number. Ongoing fiber photometry studies indicate that semaglutide modifies dopamine dynamics during both the beginning and end of running bouts. These results expand our understanding of the broader behavioral effects of GLP-1 receptor agonists and identify potential mechanisms by which semaglutide modifies reward-related behaviors.

10:30

Targeting Stress Axes To Enhance The Therapeutic Efficacy Of Glp-1R Agonists.
Jessica M. Sa^1,2, Karen A. Scott^1,2, Todd E. Golde³, Eric G. Krause^1,2, Annette D. de Kloet^1,2
¹1Neuroscience Institute, College of Arts and Sciences, Georgia State University, Atlanta, GA, United States, ²Center for Neuroinflammation and Cardiometabolic Diseases, Georgia State University, Atlanta, GA, United States, ³Department of Pharmacology and Chemical Biology, Department of Neurology, Emory Center for Neurodegenerative Disease, Emory University, Atlanta, GA, United States

Obesity is highly prevalent worldwide. While glucagon-like peptide 1 receptor (GLP-1R) agonists reduce body weight in the short term, side effects (e.g., lean mass loss) and a tendency for individuals to regain fat mass after withdrawal limit their long-term benefit. We hypothesize that hypothalamic-pituitary-adrenal (HPA) axis dysregulation contributes to these limitations. GLP-1R agonists activate the HPA axis and corresponding increases in glucocorticoids (CORT) alter food intake and body composition. We use a novel anti-corticotrophin-releasing hormone (CRH) immunotherapy (CTRND05) to test whether dampening HPA axis activity enhances and sustains quality weight loss during and following semaglutide. Male and female C57BL/6J mice were rendered obese on high fat diet, housed in an indirect calorimetry system and assigned to four groups: 1) saline, 2) semaglutide (40ug/kg/d sc), 3) CTRND05 (25 mg/kg ip, followed by weekly 12.5 mg/kg), or 4) combination semaglutide/CTRND05. Metabolic parameters, plasma CORT and glucose tolerance were assessed prior to, during and following 3 weeks of semaglutide.As expected, CTRND05 reduced plasma CORT throughout the study.Semaglutide, alone and in combination with CTRND05, reduced body and fat mass. Furthermore, semaglutide resulted in considerable loss of lean mass, an effect abated by CTRND05. After discontinuing semaglutide, mice exhibited pronounced hyperphagia and regained adiposity. Both hyperphagia and adipose mass regain were mitigated by combined treatment with CTRND05. Collectively, these results indicate that the negative side effects of GLP-1R agonists can be mitigated by suppressing HPA axis activity, and further suggest that quality weight loss can be enhanced and sustained by interventions that lower circulating CORT.

11:00

Can Weight Loss Drugs Reduce Alcohol Consumption?
Mette Kruse Klausen
Psychiatric Centre Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen University Hospital Frederiksberg, Frederiksberg, Denmark

Alcohol use disorder (AUD) is a chronic relapsing brain disorder characterised by loss of control of alcohol intake, compulsive alcohol behaviour leading to relapse, and a negative affective state when not consuming alcohol. Globally, AUD is a tremendous burden, with an estimated 280 million people suffering from this disorder, and the treatment gap is wide compared to other mental health disorders. In this perspective, AUD is a severe condition with enormous consequences for the individual, relatives, and society, and is regarded as the most harmful addictive drug when taking harm to both the user and others into consideration. According to clinical guidelines, a combination of psychological intervention and pharmacological treatment is recommended in patients with moderate to severe AUD. However, only three drugs are approved by the U.S. Food and Drug Administration. In the search for novel treatment strategies for AUD, glucagon-like peptide-1 (GLP-1) receptor agonists approved for treating type 2 diabetes and obesity have caught much attention. GLP-1 is a naturally occurring peptide produced in the small intestines and in the brain, regulating glucose homeostasis, feeding, and body weight. Importantly, recent research demonstrates that GLP-1 also acts within brain regions involved in reward and addiction. This session will introduce the present data from preclinical studies, register-based cohort studies, brain imaging, and clinical data, all supporting the role of GLP-1 receptor agonists as a novel treatment of alcohol use disorder.

10:00

Anatomical And Functional Architecture Of Brainstem Interoceptive Pathways
Chen Ran
The Scripps Research Institute, San Diego, CA, United States

The nucleus of the solitary tract (NTS) in the brainstem serves as the brain's primary interoceptive hub. It integrates and processes convergent sensory inputs from visceral organs via the vagus nerve and spinal cord, transmitting signals to higher-order brain regions to regulate behavior, physiology, and metabolism. Despite its importance, the principles by which the NTS organizes peripheral information to mediate these complex responses remain poorly understood. We develop a novel in vivo two-photon brainstem imaging platform, which allows us to record the activities of thousands of NTS neurons simultaneously. We discover that the NTS creates a map of internal organs that takes the shape of a "visceral homunculus". This topography requires brainstem inhibition, as blockade of inhibition broadens neuronal tuning and disrupts spatial organization. Combining brainstem imaging with genetic strategies to label targeted populations of NTS neurons, we show that the NTS creates parallel viscerosensory pathways. These pathways are distributed across the topographic map of internal organs and are similarly tuned to respond to various viscerosensory stimuli but differentially control behavior and metabolism. Our work establishes the conceptual framework of the organizational logic of the brainstem interoceptive circuits.

10:15

Vagal Sensory Neurons Selectively Encode Intestinal Protein
Alan de Araujo^1,2, Mingxin Yang^1,2, Avnika Bali^1,2, James McCutcheon⁴, Christopher Morrison³, Guillaume de Lartigue^1,2
¹Monell Chemical Senses Center, Philadelphia, PA, United States, ²University of Pennsylvania, Philadelphia, PA, United States, ³Pennington Biomedical Research Center, Baton Rouge, LA, United States, ⁴UiT the Arctic University of Norway, Tromso, Norway

Dietary protein is essential for survival and generally palatable, though less reinforcing than fats or sugars. When protein intake is restricted, animals rapidly increase consumption of protein-rich foods, suggesting that animals can detect protein deficiency and adapt their intake accordingly. However, the neural circuits that sense ingested protein and guide this adaptive behavior remain poorly defined. We hypothesized that a specific population of vagal sensory neurons detects dietary protein and transmits this signal to the brain to influence protein appetite. Results: To manipulate protein status, mice were maintained on a low-protein diet (5% casein) to induce a protein-depleted state, or a control diet (20% casein) to maintain protein repletion. In vivo calcium imaging of the nodose ganglia revealed that intestinal casein infusion activates a subset of vagal sensory neurons, with enhanced responses in protein-depleted mice (n=382-512 neurons, p<0.05). Consistently, within-animal FosTRAP mapping revealed greater NTS activation in response to casein infusion during protein depletion compared to repletion (n=5). In two-bottle behavioral tests, control mice increased casein intake when protein-depleted (p<0.05). Mice lacking protein-sensing vagal neurons exhibited elevated casein consumption regardless of diet, suggesting impaired detection of protein status. Upon switching from a depleted to a replete diet, control mice reduced casein intake (p<0.01), with females adapting to changes in protein status quicker than males (7 vs 14 days). In contrast, ablated mice failed to adapt at all time points (p<0.05). Conclusion: These findings identify a vagal gut-brain pathway that detects dietary protein and influences protein appetite through post-ingestive feedback.

10:30

A Dedicated Gut-Brain Pathway For Hypothalamic Fructose Sensing
Aaron D Mcknight^1,2, Fang Y Hsu², Alexandra G Vargas², Alan Araujo², Guillaume Lartigue^1,2, Amber L Alhadeff^1,2
¹Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, United States, ²Monell Chemical Senses Center, Philadelphia, PA, United States

Activity in hypothalamic agouti-related protein (AgRP)-expressing neurons drives food intake and is inhibited by the post-ingestive detection of calories. Given that our modern diets contain increasing levels of added sugars, we examined how glucose and fructose impact activity in AgRP neurons. We monitored AgRP neuron activity using in vivo fiber photometry, and surprisingly found that equicaloric quantities of fructose (8% and 16% w/v, 1 ml intestinal infusion) were much less effective than glucose at inhibiting AgRP neuron activity (n=10, two-way ANVOA p<0.05). The time to maximally inhibit AgRP neuron activity was longer after fructose compared to glucose infusion, suggesting that fructose may modulate AgRP neurons in a paracrine fashion (n=10, two-way ANOVA p<0.05). Therefore, we measured levels of satiation hormones after a gastric infusion of either sugar and found that fructose evokes 10-fold higher levels of plasma peptide YY (PYY) than glucose (n=11-13/group, one-way ANOVA p<0.0001). Pretreatment with a systemic (paired t-test p<0.05), but not centrally-infused (n=6, paired t-test p=ns), Y2 receptor antagonist, or elimination of vagal signaling by subdiaphragmatic vagotomy (n=4-6/group, unpaired t-test p<0.05) abolished fructose, but not glucose, -induced inhibition of AgRP neuron activity. Finally, in vivo imaging of vagal afferents revealed distinct subpopulations that are activated (defined as mean z-score during stimulation>2.5 from baseline median) to either fructose (n=45) or glucose (n=56), with few (n=13) neurons responding to both. Therefore, our data reveal that fructose engages a distinct gut-to-hypothalamic pathway and is less effective than glucose at inhibiting AgRP neurons, a finding that may impact feeding behavior and obesity development.

10:45

Sex-Specific Differences In Postprandial Satiety Signaling After A Sugar-Reduced Sucrose Solution While Maintaining Sweetness Level
Marlies Gaider^1,3,6, Isabella Kimmeswenger^2,3, Jana Medek¹, Moritz Gaupp¹, Jakob P. Ley⁴, Gerhard E. Krammer⁴, Veronika Somoza⁵, Barbara Lieder^1,2,6
¹Christian Doppler Laboratory for Taste Research, Faculty of Chemistry, University of Vienna, Vienna, Austria, ²Institute of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria, ³Vienna Doctoral School of Chemistry (DoSChem), Vienna, Austria, ⁴Symrise AG, Holzminden, Germany, ⁵Leibniz Institute for Food Systems Biology at the Technical University of Munich, Freising, Germany, ⁶Institute of Clinical Nutrition, University of Hohenheim, Stuttgart, Germany

Sweetness perception is discussed to interfere with postprandial glucose and insulin regulation. This study examined whether maintaining perceived sweetness while reducing the sucrose content of a test solution affects incretin hormone secretion and blood sugar control with consequences for energy intake and whether sex-specific differences exist. We hypothesized that the carbohydrate content plays a stronger role than the perceived sweetness for inducing postprandial satiety signaling. In a single-blinded, randomized crossover study, 39 healthy participants (21 female, 18 male), consumed a 10 % sucrose solution, an equi-sweet tasting 7 % sucrose solution with 50 mg/L hesperetin and a less sweet tasting 7 % sucrose solution. Blood samples were collected at baseline and 15, 30, 60, 90 and 120 minutes postprandial and energy intake was assessed using a standardized ad liibitum breakfast 2 hours postintervention. Female participants exhibited lower glucose peaks after consuming the sucrose-reduced solutions. However, males reached similar glucose peaks independent of the test solution, explained by higher insulin concentrations following the 10 % sucrose solution. GLP-1 concentrations were higher in females after consuming the 10 % sucrose and hesperetin-spiked solutions but remained unaffected in males. In contrast, GIP levels were higher in males after the two equi-sweet solutions compared to the 7% sucrose treatment. Energy intake did not differ between the different treatments. Our findings demonstrate sex-specific differences in postprandial glucose regulation and incretin hormone responses. However, maintaining sweetness level while reducing sucrose content did not adversely affect satiety signaling or energy intake in both female and male participants.

11:00

Temporal Control Of Snacking And Body Weight By Ghsr-Expressing Suprachiasmatic Nucleus Neurons
Omprakash Singh^1,2, Sepideh Sheybani-Deloui¹, Soumya Kulkarni¹, Moyu Lyu¹, Bingbing Li¹, Salil Varshney¹, Kripa Shankar¹, Deepali Gupta¹, Luis Leon Mercado¹, Avi W. Burstein¹, Corine P. Richard¹, Connor Lawrence¹, Sherri Osborne-Lawrence¹, Jeffrey M. Zigman^1,2,3
¹Center for Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States, ²Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX, United States, ³Division of Endocrinology & Metabolism, Department of Internal Medicine, UT Southwestern Medical Center,, Dallas, TX, United States, ⁴Department of Psychiatry, UT Southwestern Medical Center,, Dallas, TX, United States

Food consumption impacts body weight differently depending on time-of-day. Exemplifying this concept, providing mice or people food during their usual circadian rest phase (light cycle for mice; night-time for people) leads to greater body weight gain than providing it during the active phase. This suggests the existence of specific neurocircuitry that impacts eating and body weight in a manner dependent on circadian phase/time-of-day. One such neurocircuit may reside in the suprachiasmatic nucleus (SCN), the body’s central circadian pacemaker. Here, we tested the hypothesis that SCN neurons responsive to the orexigenic hormone ghrelin temporally regulate eating and body weight in mice. Chemogenetic stimulation of GHSR (ghrelin receptor)-expressing SCN neurons during the mid-circadian rest phase (10AM-2PM) - which is a period of low ghrelin resistance - increased food intake by 144% (p<0.05; n=4; paired Student’s t-test). Repeated chemogenetic inhibition of these neurons during this same time-of-day reduced (by 35%) the corresponding, typically low level of food intake reminiscent of snacking; it also reduced body weight (by 7%) (p<0.05; n=6-9). These effects were not observed at other times-of-day. Chemogenetic stimulation of GHSR-expressing arcuate hypothalamic neurons also increased food intake, although independently of time-of-day (p<0.05; n=3-4). GHSR-expressing SCN neurons represented subpopulations of six distinct SCN neuronal clusters, were predominantly GABAergic, and exhibited light-sensitive, time-of-day-dependent transcriptomic profiles. Thus, our study identifies GHSR-expressing SCN neurons as a neuronal population that regulates snacking during the mid-circadian rest phase and accounts for a small but not insignificant proportion of a mouse’s body weight.

11:15

From Stomach To Striatum: Ghrelin Infusions Increase Work For Rewards
Corinna Schulz^1,2, Franziska Peglow¹, Christian La Fougere³, Benjamin Bender⁴, Johannes Klaus¹, Martin Walter^5,6,7, Matthias Reimold³, Nils B Kroemer^1,2,8
¹Department of Psychiatry and Psychotherapy, Tuebingen Center for Mental Health, University of Tuebingen, Tuebingen, Germany, ²Section of Medical Psychology, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Bonn, Bonn, Germany, ³Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, University of Tuebingen, Tuebingen, Germany, ⁴Diagnostic and Interventional Neuroradiology, Department of Radiology, University of Tuebingen, Tuebingen, Germany, ⁵Department of Psychiatry & Psychotherapy, University Hospital Jena, Jena, Germany, ⁶Department of Behavioral Neurology, Leibniz Institute for Neurobiology, Magdeburg, Germany, ⁷German Center for Mental Health (DZPG), partner site Jena-Magdeburg-Halle, Germany, ⁸German Center for Mental Health (DZPG), partner site Tuebingen, Germany

Preclinical evidence demonstrates that the stomach-derived hormone ghrelin increases work for food via the dopaminergic system. However, translational research in humans is scarce, and it is not known if surges of ghrelin acutely boost motivation via increases in dopamine. To close this gap, we investigated the effects of acyl ghrelin infusions (vs. saline) on instrumental work for rewards, functional connectivity (FC), and dopamine transmission using a double-blind, randomized crossover study with ¹¹C-raclopride PET-fMRI in 26 healthy human volunteers. First, ghrelin increased subjective ratings of hunger (b = 15.87, p = .007) and instrumental effort for food (b = 2.12, p = .045) as well as small rewards (b = 2.80, p = .043), indicative of a shift in motivation. Second, we tested if ghrelin enhanced hypothalamic or nucleus accumbens (NAcc) seed-based FC. Ghrelin increased FC between the hypothalamus and striatal regions (NAcc: t_max = 3.36, p_SVC = .016; caudate: t_max = 3.79, p_SVC = .019), as well as within the striatum (NAcc-putamen: t_max = 4.78, p_SVC = .001), demonstrating an enhanced coupling between homeostatic and motivational circuits. Third, we investigated if ghrelin decreased striatal dopamine binding potential (BP_ND) which would reflect increases in endogenous dopamine tone. Although ghrelin increased BOLD responses in the midbrain during effort (t_max = 4.10, p_SVC = .002), it did not alter BP_ND in the striatum (N = 20, sample will be completed), suggesting that ghrelin does not durably increase striatal dopamine tone. We conclude that ghrelin’s effects on motivation show an increase in the value of work for rewards, specifically food, highlighting the potential of targeting gut-brain interactions to improve motivational symptoms, such as loss of appetite.

11:30

Innovation Through Collaboration - Novo Nordisk Partnership Models
JOERG HOECK
Novo Nordisk A/S

11:45

Open Science And Open Source Tools Seminar

1:00

Functional Properties Of The Cephalic-Phase Insulin Response In Mice
John Glendinning
Barnard College, Columbia University, New York, NY, United States

Mammals have evolved a variety of feed-forward mechanisms that minimize disturbances to their internal milieu. For example, to limit the rise in blood glucose during and after meals, mammals elicit rapid increases in celiac artery blood flow, celiac artery vascular conductance, and insulin secretion. Because these responses are triggered by stimulation of sensory systems in the head (e.g., vision, olfaction and taste), they are called cephalic-phase responses. Over the past decade, my colleagues and I have examined the functional properties of the cephalic-phase insulin response (or CPIR) in mice. I will address five facets of this work. (1) What is the physiological significance of CPIR? We determined that (as in other mammals) CPIR markedly enhanced glucose tolerance. We also observed large individual differences in CPIR magnitude, and that those mice with larger CPIR magnitudes exhibited better glucose tolerance. (2) Does CPIR magnitude vary with diet? We discovered that CPIR magnitude and glucose tolerance increased with carbohydrate content of the diet. (3) What stimuli elicit CPIR? In naïve mice, we found that CPIR could be elicited by oral stimulation with glucose or glucose-containing carbohydrates, but not with fructose, sweeteners or novel types of mouse chow. (4) To what extent can CPIRs be conditioned? We found that mice could condition CPIRs to mouse chows and to flavors associated with the post-oral actions of concentrated glucose. (5) When mice condition a CPIR to one food, does it generalize to other foods? We discovered that a conditioned CPIR to one type of chow did not generalize to another type of chow with the same macronutrient composition. The latter finding revealed a high degree of diet specificity in the CPIR conditioning process.

2:00

Relationships Between Increasing Pre-Load Meal Size, Post-Prandial Plasma Acyl Ghrelin, Appetite, And Food Intake In Adults Without Obesity - Is Ghrelin A Human Satiety Signal? (George H. Collier New Investigator Travel Awardee)
Tasya Parastika¹, Jiaxyn Liu¹, Raghav Bhargava¹, Wai In Ng¹, Jialin Guo¹, Marcela Rodriguez Flores¹, Xinyi Zhang¹, Mimoza Emini¹, Wanqian Li¹, Sandra Luur¹, Zoe Barley¹, Jeff Brunstrom², Anthony P Goldstone¹
¹PsychoNeuroEndocrinology Research Group, Division of Psychiatry, Department of Brain Sciences, Imperial College London, London, United Kingdom, ²School of Psychological Science, University of Bristol, Bristol, United Kingdom

Background: Stomach-derived acyl ghrelin (AG) stimulates human appetite/food intake from studies of supra-physiological AG administration, but correlational studies of endogenous plasma AG with eating behaviour are contradictory. Plasma total ghrelin falls with increasing pre-load meal size in adults without obesity, but it is unclear if this contributes to post-prandial attenuation of eating behaviour. Methods: In a randomised, single-blinded study, n=17 adults without obesity (53% male, age 21-55 years) attended 4 visits after an overnight fast, consuming 750mL liquid preloads 0, 600, 900, 1200 kcal. At 0, 0.5, 1, 2, 3h plasma AG was assayed, and appetite and food craving ratings completed (n=17, 65 visits). At 2h a virtual portion size creation task measured desired food intake (n=15, 57 visits), and at 3h an ad libitum meal measured actual food intake (n=10, 39 visits), with data excluded for those participants with intake <20% estimated REE at 0 kcal visit. Results: Pre-load meal size correlated negatively with post-prandial changes (iAUC_0-2/3h) in appetite, craving, desired and actual caloric intake (r=-0.55 to -0.38, P=0.010 to <0.001). Plasma AG iAUC_0-3hnegatively correlated with pre-load size (r=-0.53, P<0.001) and positively correlated with post-prandial changes in appetite/craving (r=0.33-0.34, P<0.005), desired (r=0.33, P<0.005), and actual (r=0.26, P<0.05) food intake. Conclusion: The post-prandial fall in plasma AG may contribute to the greater attenuation of eating behaviour with increasing preload meal size in adults without obesity, supporting a role for changes in plasma AG as a human satiety signal. Ongoing assay of plasma hormone LEAP2, an inverse agonist at ghrelin receptor (GHSR), is examining its additional potential as a satiety hormone by impacting GHSR signalling.

P2
2:15

A Cerebellar Memory Of A Meal (New Investigator Travel Awardee)
A-Hyun Jung¹, Aloysius Y.T. Low¹, J. Nicholas Betley^1,2
¹Department of Biology, University of Pennsylvania, Philadelphia, PA, United States, ²Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, United States

Cerebellar output neurons have recently been shown to regulate food intake. To further explore the function and characteristics of cerebellar output neurons activated during the course of the meal, we used Fos-TRAP technology to permanently label neurons in the cerebellum activated by a meal. We used Fos^2A-iCreER mice to express chemogenetic actuators or calcium indicators in the lateral deep cerebellar nuclei (latDCN) neurons activated during high fat diet refeeding after 24hr fasting. Chemogenetic activation, but not inhibition, of the latDCN meal engram reduced the food intake in 1hr and 3hr food intake measures. Importantly, activating the latDNC meal engram did not affect energy expenditure in metabolic chamber or motor functioning in motor activity assessments. Using fiber photometry calcium imaging, we found that neural activity in the latDNC meal engram is suppressed while the mice eat food pellets. Notably, intraperitoneal injection of post-prandial hormone insulin and CCK, but not the hunger hormone ghrelin, activated the latDCN meal engram. Glucose and 2-DG injection, which both increase plasma glucose level, raised the activity of latDCN meal engram neurons. Fluorescence in situ hybridization showed that the latDCN meal engram neurons highly express vGLUT2 and SPP1. Together, these results characterize a population of latDCN neurons that comprise a memory of a meal.

P3
2:30

Resilience Amidst Adversity: How Adverse Childhood Experiences And Protective Factors Influence Body Weight Status In Latinx/Hispanic Youth (New Investigator Travel Awardee)
Victoria Goldman¹, Sevan Esaian¹, Jonatan Ottino Gonzalez¹, Miguel A. Rivas Fernandez¹, Nicole R. Karcher², Jeffrey I. Gold¹, Alaina P. Vidmar¹, Shana Adise¹
¹Children's Hospital Los Angeles, Los Angeles, CA, United States, ²Washington University School of Medicine, St. Louis, MO, United States

Adverse childhood experiences (ACEs) may contribute to rising youth obesity rates through stress-induced weight gain via hormonal dysregulation and altered food intake. Few studies have explored this association in youth including what protective factors (PF) may mitigate it. Even less is known about these associations in Latinx/Hispanic (LH) communities, despite higher ACEs and obesity rates. Using the Adolescent Brain Cognitive Development Study (n=5,435; age 11-12; 51% male; 21% LH), we explored associations between ACEs, PF, and BMI. We hypothesized that higher ACEs would be associated with greater BMI but weakened by PF (youth-reported self-coping, friend or caregiver support). We anticipated stronger findings in LH youth. ACEs comprised 12 categories (e.g., sexual abuse, bullying) from caregiver or youth answers, summed to a total score. Linear mixed-effects examined ACE*Ethnicity (LH vs. non-LH)*PF on BMI, controlling for age, sex, puberty, socioeconomic status and study site. We found that higher ACEs were associated with greater BMI (β_LH=0.56; β_non-LH=0.38, p<0.001). LH youth had greater BMI (22.1+5kg/m²) and ACEs (2.1+1.7) than non-LH youth (BMI=20.3+4.6kg/m²; ACEs=1.7+1.7; p<0.001). In LH youth only, self-coping (β=-0.65) and caregiver-support (β=-0.33) moderated the ACE-BMI relationship (p’s<0.05). Our findings suggest ACEs increase youth obesity risk, while two PF weaken the ACE-BMI relationship in LH youth. This highlights the importance of promoting culturally informed, resiliency-focused skills like self-coping and positive adult relationships, particularly among LH-youth experiencing ACEs. Early ACE screening to identify at-risk youth, coupled with PF promotion and trauma-informed weight interventions, may help improve pediatric weight trajectories.

P4
2:45

Improved Food Approach Following Weight Restoration With Meal-Based Behavioral Treatment In Inpatients With Anorexia Nervosa. (New Investigator Travel Awardee)
Sarah H Guo¹, Joseph McGuire¹, Jeffrey M Brunstrom², Timothy H Moran¹, Angela Guarda¹, Kimberly R Smith¹
¹Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, United States, ²School of Psychological Science, University of Bristol, Bristol, United Kingdom

Individuals with anorexia nervosa (AN) often experience marked anxiety when consuming high energy-dense (HED) foods. This anxiety leads to the avoidance of HED foods, which interferes with recovery. Weight restoration is the strongest predictor of recovery and remission in AN. Despite treatment advances, empirical evidence of changes in food preference and consumption during recovery remains limited. The Johns Hopkins Eating Disorders Inpatient Program employs a meal-based behavioral protocol to increase consumed food variety and achieve rapid weight restoration. We recruited women with AN (N=21) admitted to this program to determine the effect of a meal-based approach on food liking and wanting, anxiety-to-eat, perceived maximum tolerable portion size and food healthiness. Following an overnight fast, participants completed a computer task featuring images of 10 HED and 10 low energy-dense (LED) foods across five portion sizes (standard * 0.25, 0.5, 1, 2, 4) on two occasions: shortly after hospital admission (T1) and again upon reaching weight restoration (T2). At T2, participants reported increases in the consumption of and maximum tolerable portion size of HED foods. This change was accompanied by increased wanting for and decreased anxiety-to-eat HED foods. For LED foods, anxiety-to-eat decreased while wanting remained unchanged. Food liking and perceived healthiness of HED and LED foods did not change with weight restoration. These findings suggest that meal-based nutritional and behavioral interventions targeting increased variety of HED and LED food intake may improve food approach (reduce anxiety-to-eat, increase wanting) while maintaining food stable perception (liking, healthiness) in individuals with AN hospitalized for acute weight restoration.

P5
3:00

From Metabolism To Memory: Exploring Amylin'S Role In The Hippocampus (New Investigator Travel Awardee)
Giulia Mazzini¹, Irmak Gezginer^2,3, Gaia Serra¹, Diana Kindler², Christelle Le Foll¹, Daniel Razansky^{2, 3}, Thomas A. Lutz¹
¹Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland, ²Institute for Biomedical Engineering and Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Zurich, Zurich, Switzerland, ³Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, ETH , Zurich, Switzerland

Amylin, a hormone co-secreted with insulin by pancreatic β-cells in response to nutrient intake, acts as a satiation signal. Amylinomimetics are approved treatments for diabetes and in the future most likely for obesity management thanks to their effects on appetite and glucose metabolism. Although amylin's effects on eating behavior are well-documented, its broader physiological functions still need to be uncovered. Here, we investigated amylin's role in hippocampal function and memory processing. Using resting-state fMRI, we examined how amylin (500 µg/kg) and a long-acting amylin receptor agonist salmon calcitonin (sCT; 10 µg/kg) affect hippocampal connectivity in wild-type (WT) mice compared to knock-out (KO) mice lacking amylin receptor fundamental components (RAMP1/3). Both compounds induced significant changes in hippocampal connectivity patterns in WT mice but not in KO mice, highlighting the critical role of intact amylin receptor signaling in mediating these responses. c-Fos expression in the hippocampus was higher in amylin-injected and sCT-injected mice than in vehicle-injected mice, suggesting increased neuronal activation in this area. Through novel object and novel location recognition behavioral studies, we showed that amylin-treated WT mice significantly improved object recognition and spatial memory, while sCT treatment did not enhance memory performance. In a rat model both amylin- (50 µg/kg) and sCT-injected (5 µg/kg) rats demonstrated an improved ability to recognize objects and spatial locations compared to vehicle-injected rats. Our findings reveal amylin as a significant modulator of hippocampal function and memory processing, suggesting its potential therapeutic applications for both metabolic and cognitive disorders.

P6
3:15

Mapping Energy Metabolism Pathways In The Human Brain (Elsevier Appetite New Investigator Travel Awardee)
Moohebat Pourmajidian¹, Justine Y. Hansen¹, Golia Shafiei², Bratislav Misic¹, Alain Dagher¹
¹McGill University, Montreal, QC, Canada, ²McGill University, Montreal, QC, Canada, ³University of Pennsylvania, Philadelphia, PA, United States, ⁴McGill University, Montreal, QC, Canada, ⁵McGill University, Montreal, QC, Canada

Energy metabolism consists of a set of biological pathways that produce ATP using nutrients such as glucose and oxygen. These pathways also provide biomolecules critical for cellular growth and repair, making them integral to our understanding of brain structure and function. Despite extensive studies on brain glucose uptake, the organization of downstream glucose metabolic pathways in the cortex remains largely unexplored. Here, we use whole-brain transcriptome data from 6 donors (1 female, 24-57 years) in the Allen Human Brain Atlas to study spatial cortical profiles of key energy pathways including glycolysis, pentose phosphate pathway, tricarboxylic acid cycle, oxidative phosphorylation and lactate metabolism. We create regional mean-expression maps of these pathways across the cortex using pathway-specific gene expression data. We show that energy pathways exhibit heterogenous cortical gene expression, with a dichotomy between primary ATP-producing pathways and the anabolic pentose phosphate pathway in the primary motor and sensory cortices, reflecting information processing hierarchy. These maps also exhibit unique relationships with the cellular and laminar organization of the cortex, pointing to higher energy demands of large pyramidal cells. Finally, we show that energy pathways exhibit unique developmental trajectories using a lifespan transcriptomics dataset of the human brain (42 donors, 19 female, 8 post conception weeks-40 years). The main ATP-producing pathways peak in childhood, tracking cortical volume, while the pentose phosphate pathway shows greater prenatal expression and declines in later life, mirroring brain tissue biosynthesis. Collectively, this study provides insight into the metabolic makeup of the human brain and its developmental demands.

P7
3:30

The Estrous Cycle Moderates The Food And Body Weight Suppressive Effects Of Glucagon-Like Peptide-1 Receptor Agonism (Randall R. Sakai New Investigator Travel Awardee)
Sarah V Applebey, Allison G Xiao, Matthew R Hayes
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

Among young adults, women largely drive demand for weight loss pharmacotherapies targeting the glucagon-like peptide-1 receptor (GLP-1R). Clinical trials for many GLP-1R analogs (GLP-1RAs) have revealed a curious sex difference: women lose a greater percentage of weight compared to men. Despite the popularity of GLP-1RAs, the mechanism(s) underlying women’s enhanced weight loss is unclear. Recently, we identified evidence pointing to the estrous cycle as a mediator of this effect. In female rats, expression of Glp1r and the GLP-1 precursor gene, Gcg, increased during two estrous phases, proestrus and estrus (P/E), compared to males and compared to other estrous phases, metestrus and diestrus (M/D). These expression changes occurred in the nucleus tractus solitarius and area postrema within the brainstem’s dorsal vagal complex (DVC), an intriguing finding given the necessity of DVC GLP-1Rs in the weight loss effects of GLP-1RAs. We hypothesized that greater endogenous GLP-1 or GLP-1R during P/E may potentiate effects of GLP-1RAs. To examine whether the estrous cycle impacts efficacy of GLP-1RAs, we administered acute liraglutide and chronic semaglutide during either P/E or during M/D in female rats on high fat diet. In both studies, injections during P/E enhanced the intake-suppressive effects of GLP-1RAs. Moreover, chronic semaglutide administration during only P/E led to pronounced body weight loss compared to M/D administration. We also identified additional nuclei throughout the neuraxis that showed greater in Glp1r expression in P/E. Together, our findings highlight the estrous cycle’s ability to impact brain GLP-1R signaling and may have translational implications for timing of GLP-1RA administration across the ovarian cycle in premenopausal women. NIH-DK137443

P8
3:45

Dietary Protein Intake Is Negatively Associated With Energy Intake But Not With Body Mass Index In A Population-Based Norwegian Sample: The Tromsø Study 2015-2016 (Dorothy W. Gietzen New Investigator Awardee)
Rikke Eriksen¹, Kamilla Rognmo¹, Laila A. Hopstock², James E. McCutcheon¹
¹Department of Psychology, UiT The Arctic University of Norway, Tromso, Norway, ²Department of Health and Care Sciences, UiT The Arctic University of Norway, Tromso, Norway

The protein leverage hypothesis proposes that the obesity epidemic is driven by the essential need to obtain sufficient dietary protein. In diets that contain low levels of protein, a leveraging mechanism will cause overconsumption of foods high in carbohydrate and fat as people attempt to reach their protein target. Ultra-processed foods (UPFs) may be involved in this process as they cause dilution of protein content in the western food supply. We investigated these phenomena using cross-sectional data from a large Norwegian population-based study, The Tromsø Study 2015-2016. We examined the relationship between dietary protein intake, total energy intake, body mass index (BMI), and the role of UPFs in a sample of inhabitants of the municipality of Tromsø, Norway (n = 11,152; 40-99 years; 53% women). Fitted power functions revealed partial protein leverage as indicated by a negative L-value (L = -0.36, p <.001), such that total energy intake decreased as the proportion of dietary protein increased. However - and contrary to the protein leverage hypothesis – the relationship between BMI and dietary protein was weak and positive (b = 0.01; p <.001), as tested with linear regression. Further, as the proportion of UPFs in the diet increased, dietary protein (%) decreased (b = -1.8; p <.001), while total energy intake (kJ) increased (b = 1,999; p <.001), a finding that supports the protein leverage mechanism. Finally, a high proportion of UPFs was related to a higher BMI (b = 0.01; p = .037), however, this effect was minimal. In summary, our study of middle-to-older aged Norwegians provides strong support for the protein leverage mechanism but no evidence for an effect of protein leverage on BMI.

10:00

High-Fat Diets Attenuate Nucleus Accumbens Dopamine Release And Enhance Nicotine Reinforcement-Related Behavior In Mice
Samuel Tetteh-Quarshie, Lauren E Young, Brandon J Henderson
Joan C Edwards School of Medicine at Marshall University, Huntington, WV, United States

Smoking and obesity are the leading causes of preventable deaths in the United States. However, studies examining the synergistic effects of obesity and smoking (including vaping) in preclinical models are sparse. Based on previous investigations, we hypothesized high-fat (obesogenic) diets alter nicotine reinforcement by attenuating dopamine (DA) release. Male and female mice (n=6 each) were exposed to vaporized nicotine after being maintained on a regular rodent diet (RD; 5% fat) or obesogenic diets (DIO; 42% or 60% fat) for 6 weeks. DA release in the nucleus accumbens core (NAcc) was assessed with fast-scan cyclic voltammetry (FSCV). We further examined whether obesity-induced neuroadaptation in the dopaminergic system modulates nicotine reinforcement-related behaviors. Here, a separate cohort of RD and DIO mice (n = 6, each condition, each sex) were trained to self-administer nicotine using an e-vape® self-administration (EVSA) assay. Obesogenic mice exhibited reduced tonic and phasic dopamine release in the NAcc and displayed a significant increase in nicotine reinforcement-related behaviors (two-WAY ANOVA). To examine circuit inputs into the VTA, we used patch-clamp electrophysiology to examine changes in intrinsic excitability in the medial prefrontal cortex (mPFC) and VTA. Here, we observed that VTA DA neurons exhibited a diet-induced decrease in excitability but layer 5 pyramidal neurons in the mPFC exhibited a diet-induced increase in excitability (t test). The data presented here suggest that obesogenic diet enhances nicotine reinforcement-related behaviors, and this may be modulated by disturbances in the metabolic system and neuroadaptation in neuronal physiology.

10:30

Eating A High Fat/High Carbohydrate Or Ketogenic Diet Impacts Sensitivity Of Rats To The Effects Of Morphine
Katherine M Serafine¹, Nina M Beltran¹, Vanessa Minervini²
¹University of Texas at El Paso, El Paso, TX, United States, ²Creighton University, Omaha, NE, United States

Eating a high fat/high carbohydrate diet has been linked to weight gain, while eating a high fat/low carbohydrate (ketogenic) diet leads to weight loss. It has been established that high fat diet consumption increases sensitivity of rats to stimulant drugs, but it is not known if sensitivity to opioids is also impacted by diet. To test the hypothesis that eating a high fat diet would increase sensitivity of rats to the effects of morphine, male rats (n=7-8/group) ate either a low fat diet, a high fat/high carbohydrate diet, or a ketogenic diet and morphine-induced antinociception was measured using the warm water tail withdrawal procedure (0.32-56 mg/kg; IP). Tolerance was induced by administering twice-daily injections of morphine for 19 days (3.2-56 mg/kg; IP). Tail withdrawal latencies were converted to a % maximum possible effect, averaged, and analyzed using mixed model ANOVAs. Several withdrawal signs were evaluated after naltrexone administration (17.8 mg/kg; SC), including weight loss and vocalization, and were averaged and analyzed using mixed model ANOVAs. There were no differences in the acute antinociceptive effects of morphine among rats eating different diets. However, tolerance was significantly greater for rats eating the high fat/high carbohydrate diet as compared to rats eating the ketogenic diet. Following naltrexone administration, withdrawal signs were more frequent, and body weight loss was more severe for rats eating the high fat/high carbohydrate diet as compared to rats eating the ketogenic diet. These results indicate that eating a high fat/high carbohydrate diet enhances morphine tolerance, while a ketogenic diet reduces the severity of withdrawal and will be discussed in the context of chronic pain treatment, as well as opioid use disorder.

11:00

Responding For Opioids Is Reduced In Rats And Humans By Treatment With A Glucagon-Like Peptide-1 Receptor Agonist
Patricia Sue Grigson¹, Scott Bunce², Timothy Brick³, Christopher Freet², Erin Deneke⁴, Jennifer Nyland¹, H. Harrington Cleveland³, Sarah Ballard¹, Dean Stankoski⁴, Adam Scioli⁴, Joaquin Douton¹, Luke Urbanik¹, Brianna Evans¹, Christopher Brandl¹, Caleb Whitfield¹, Elise Shealy¹
¹Department of Neural and Behavioral Sciences Penn State College of Medicine, Hershey, PA, United States, ²Department of Psychiatry and Behavioral Health Penn State College of Medicine, Hershey, PA, United States, ³Department of Human Development and Family Studies Penn State University, Happy Valley, PA, United States, ⁴Department of Psychiatry and Behavioral Health Penn State College of Medicine, Hershey, PA, United States, ⁵Caron Treatment Center, Wernersville, PA, United States

Opioid use disorder (OUD) is a devastating disease, and deaths due to opioid overdose continue to rise. Effective new treatments are needed. Here we tested the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for the treatment of OUD in rodent models and in humans in residential treatment. Pre-clinical: Methods and Results. Treatment with all GLP-1RAs tested, including exendin-4, liraglutide, semaglutide, and tirzepatide reduced heroin taking and heroin and fentanyl seeking (i.e., ‘relapse’) in both male and female rats and when administered acutely or chronically. Clinical: Methods. In a fully-randomized, double-blind, placebo-controlled study, patients in residential treatment for OUD were consented following medically assisted withdrawal, stratified by patient’s choice for medication assisted treatment (MAT: buprenorphine) or No MAT, then randomized into placebo (n=10) or liraglutide (n=10) treatment conditions. Liraglutide was administered subcutaneously daily; doses were increased from 0.6 mg to 1.2 mg to 1.8 mg every 6 days, then discontinued on terminal days 20 and 21. Clinical: Safety and Efficacy. Daily treatment with liraglutide did not adversely affect body weight, blood glucose, or cardiorespiratory function in this population. Regarding efficacy, data gathered using ecological momentary assessment showed that liraglutide reduced craving by 40% compared to placebo (Cohen’s d @.5, p=0.005), even at the lowest dose (Cohen’s d @.5, p=0.005), and liraglutide treatment, compared to placebo, was associated with reduced opioid craving in the afternoon and evening (p <0.002) and during times of high stress. Conclusion. Although the sample size is small, daily treatment with liraglutide appears safe and effective in reducing craving and seeking in both animals and in humans.

10:00

Subcortical Brain Function Preferentially Aligns With An Internal Gastric Rhythm During A Food Bidding Task
Nils B. Kroemer^1-4, Vanessa Teckentrup², Ignacio Rebollo⁵, Manfred Hallschmid^3,4,6, Sophie J. Mueller²
¹Section of Medical Psychology, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Bonn, Bonn, Germany, ²Department of Psychiatry and Psychotherapy, TÃÂ¼bingen Center for Mental Health, University of TÃÂ¼bingen, TÃÂ¼bingen, Germany, ³German Center for Mental Health (DZPG), partner site TÃÂ¼bingen, TÃÂ¼bingen, Germany, ⁴German Center for Diabetes Research (DZD), Neuherberg, Germany, ⁵Department of Decision Neuroscience and Nutrition, German Institute of Human Nutrition, Potsdam, Germany, ⁶Institute of Medical Psychology and Behavioural Neurobiology, University of TÃÂ¼bingen, TÃÂ¼bingen, Germany

Eating is regulated by an integration of internal and external cues. Despite mechanistic progress in the past decades, how the brain adaptively arbitrates between interoceptive versus exteroceptive processing to regulate energy metabolism remains elusive. Here, we manipulated the influence of internal and external cues using transcutaneous vagus nerve stimulation (tVNS) and a food bidding task, while measuring brain responses and gastric myoelectric activity. To quantify the integration of these cues, we evaluated their synchronization with brain signals during rest and task conditions in 27 healthy participants (20 women; see Müller et al., 2022, Brain Stimul). Our findings reveal that subcortical regions predominantly align with internal gastric signals, whereas cortical regions synchronize with task-related external cues. Crucially, tVNS further amplifies the synchronization with gastric signals in the nucleus accumbens during the food task (vs. sham). Correlations of brain coupling with internal versus external signals with individual differences in motivation and subjective hunger support a role in appetitive behavior. Taken together, our results highlight the vital role of internal gut signals in driving subcortical brain responses and show their modulation by vagal afferents. By bypassing the need for self-reports of interoception, our innovative approach holds great promise for future translational work to understand better how eating is regulated in an adaptive or maladaptive manner.

10:15

Amygdala Projections To The Pons Promote Motor Programs Of Ingestion
Danielle Lafferty, Jeremiah Isaac, Joelyz Wolcott, Amy Phan, Andrew Lutas
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, United States

We investigated neural circuit mechanisms that allow for the overconsumption of food despite visceral satiety signals. Here we focused on the projection from the central nucleus of the amygdala (CeA) to the pons region of the hindbrain, which has been implicated in overconsumption. However, within the pons, CeA targets the parabrachial nucleus that relays visceral sensory signals as well as the nearby peritrigeminal premotor circuits that control orofacial behaviors. The contribution of these pathways to the over ingestion behavior is unknown. Using fiber photometry (n = 12) and two-photon microscopy (n = 5), we recorded the activity of CeA GABAergic axons in the pons. Axon activity levels correlated to the duration of bouts of licking for liquid food and were not modulated by physiological state or palatability, suggesting that this pathway modulates consummatory behaviors. Optogenetic activation of axons in head-fixed mice (n = 7) triggered context-specific orofacial motor behaviors, including licking and biting, as well as excessive drinking of any liquid, regardless of palatability. In freely moving, ad libitum-fed mice (n = 11), photostimulation induced biting, chewing, and swallowing which led to overconsumption of food when the stimulation occurred nearby, but not away from, food. In both head-fixed and freely moving mice, photostimulation-induced over ingestion remained sensitive to visceral signals as mice eventually stopped ingesting (n = 5). These findings support a model in which CeA axon activity in the pons enables a state of orofacial behavioral disinhibition that remains controlled by external and internal contextual cues. This disinhibition, rather than suppression of satiety signals, likely drives the overeating observed with photostimulation.

10:30

Multilevel Encoding Of Nutrient-Based Food Valuation In The Primate Amygdala
Fei-Yang Huang, Fabian Grabenhorst
Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom

Sensory and nutrient food properties shape food valuation, guiding reinforcement learning (Huang & Grabenhorst, JNeurosci, 2023) and food choice (Huang et al., PNAS, 2021) in primates. However, it remains unclear whether single neurons in the primate reward system integrate sensory and nutrient information to encode subjective food value. Primate amygdala, a key structure in value-based decision-making, receives multisensory inputs and is well-positioned to process nutrient information during food choice, but direct neuronal evidence is lacking. Here, we examined the neuronal basis of nutrient reward valuation by recording single-unit activity from 208 amygdala neurons in two male rhesus macaques (Macaca mulatta) as they chose from visual cues each linked to one of the eight drinks that differ in fat, sugar, and mouthfeel (modified with tasteless thickener). Using generalized linear regression, we identified distinct neural populations encoding fat (12.02%), sugar (15.38%) and subjective value (11.06%) during visual cue presentation. Time-resolved Structural Equation Modeling (SEM) revealed that fat and sugar content contributed to the subjective value signals and that nutrient-related neuronal activity was partially mediated by oral texture properties (viscosity, oral friction). This multilevel mediation analysis uncovered a sensory-nutrient-value structure in neural reward processing, highlighting how sensory and nutrient properties contribute to food valuation within the primate amygdala. Future studies following this nutrient-reward approach could further reveal nutritional principles governing neural reward processing and adaptative food preferences in primates.

10:45

The Addictive Potential Of Ultra-Processed Foods: Identifying Key Nutritional Predictors
Ashley N Gearhardt¹, Zach Hutelin², Emmanuel Nartey², Monica Ahrens², Mary E Baugh², Tera L. Fazznio³, Erica M LaFata⁴, Kendrin R Sonneville¹, Alexandra G DiFeliceantonio²
¹University of Michigan, Ann Arbor, MI, United States, ²Virginia Tech, Blacksburg, VA, United States, ³University of Kansas, Lawrence, KS, United States, ⁴Drexel University, Philidelphia, PA, United States

Research suggests that certain foods may trigger addictive processes, contributing to difficulties in controlling intake. Meta-analyses estimate that 14% of adults meet the criteria for addictive consumption of processed foods, similar to tobacco (18%) and alcohol (14%). However, food is a complex stimulus, and not all foods trigger addictive responses. We hypothesize that ultra-processed foods (i.e., industrial products typically high in refined carbohydrates/fat that are often engineered for maximum appeal and profitability) are most likely to exhibit addictive potential. A nationally representative sample (n=1664) completed the Yale Food Addiction Scale, which applies substance addiction criteria (e.g., loss of control, cravings, tolerance, withdrawal) to food consumption,and rated a random subset of 297 commonly consumed foods to examine which nutritional factors predict a food’s addictive potential. The foods with the highest tertile addictive rating were overwhelmingly ultra-processed (91.8%), with none being minimally processed (0%). The dataset was split into training (80%) and test (20%) sets, ensuring stratification based on the average addictiveness rating. The training set was used for 5-fold cross-validation to identify the optimal predictive model among lasso regression, extreme gradient boosting, and random forest. Random forest analysis of 171 nutritional variables identified available carbohydrates, glycemic load, and energy density as the strongest predictors of a food’s rated addictiveness based on root mean squared error. Findings suggest that energy-dense, ultra-processed foods high in refined carbohydrates may be the most addictive, guiding public health efforts to reduce compulsive consumptionof these foods, which dominate the US food market.

11:00

Contrasting Metabolic And Neural Responses To Ultra- And Minimally Processed Foods.
Zach Hutelin^1,2, Monica Ahrens³, Mary Elizabeth Baugh², Bert Herald², Alexandra L. Hanlon³, Alexandra G. DiFeliceantonio^2,4
¹Graduate Program in Translational Biology, Medicine, and Health, Blacksburg, VA, United States, ²Fralin Biomedical Research Institute, Roanoke, VA, United States, ³Center for Biostatistics and Health Data Science, Roanoke, VA, United States, ⁴Department of Human Nutrition, Foods, and Exercise, Blacksburg, VA, United States

Dietary patterns have shifted toward increased consumption of ultra-processed foods (UPF), which has been linked to higher rates of preventable mortality. Although orosensory properties likely influence intake, one understudied factor is differences in post-oral signals. Here, we recruited 38 healthy weight adults aged 18-45 to examine the role of food processing on brain and metabolism. First, we performed an auction paradigm concomitant with functional magnetic resonance imaging (fMRI), where participants bid on 14 UPF and 14 minimally processed foods (MPF). Although willingness-to-pay (WTP) was not different for MPFvsUPF, BOLD response associated with WTP was greater for MPFvsUPF in the fusiform gyrus, visual cortex, thalamus, and striatum (all T>4, p<0.01). On separate days we performed two 4-hour whole room indirect calorimetry metabolic measurements with simultaneous blood draws, during which participants consumed either a UPF or MPF meal (300 kcal). Meals were matched within ~1% of energy, weight, macronutrients, fiber, and glycemic load and index. The UPF meal evoked a higher metabolic rate (p<0.05), while the MPF meal respiratory quotient (RQ) was higher (p<0.05), and there was a time by condition interaction for blood glucose (p<0.01). Next, we examined the association between post-oral signals and brain response. Difference in peak RQ was significantly associated with activation in the amygdala and ventral striatum (all T>5, p<0.03). The difference in blood glucose response at minute 20 was associated with activity in dorsomedial prefrontal and anterior cingulate cortex (all T>5, p<0.001). These data demonstrate that even matched for nutritional profile, MPF and UPF produce different post-oral signals, and those signals influence brain response to food cues.

11:15

Ultraprocessed Food Consumption Affects Structural Integrity Of Feeding-Related Brain Regions Independent Of And Via Adiposity
Arsene Kanyamibwa¹, Filip Morys², Daniel Fangstrom¹, Max Tweedale², Alexandre Pastor-Bernier², Houman Azizi², Lang Liu², Annette Horstmann¹, Alain Dagher²
¹Department of Psychology, Faculty of Medicine, University of Helsinki, Helsinki, Finland, ²Montreal Neurological Institute, McGill University, , Montreal, QC, Canada

Ultra-processed foods (UPFs) are industrial formulations with multiple ingredients that undergo extensive processing and constitute a significant portion of modern diets. UPF consumption can lead to adverse outcomes such as brain pathology (i.e., dementia) through increases in adiposity or other adiposity-independent pathways. Our study explored mechanisms by which higher UPF consumption is linked to structural brain changes, potentially contributing to a vicious cycle between diet and disease. To investigate these effects, we analyzed data from 33,654 participants (mean age at imaging assessment = 64.5 years, mean BMI = 26.09kg/m2, 17,234 women) in the UK Biobank. Using general linear model (GLM) analyses, we examined the relationship between self-reported UPF consumption and brain structure, followed by mediation analyses to explore potential pathways involving anthropometric and cardiometabolic variables. Our results indicate that higher UPF consumption is associated with changes in cellularity in the right nucleus accumbens (NAcc) and hypothalamus, as well as alterations in water content in the right NAcc. Additionally, we found that UPF consumption correlates with multiple anthropometric, metabolic, and dietary measures. These results could reflect neuroinflammation as part of a neurodegenerative process since our mediation analyses revealed that the relationship between UPF consumption and NAcc cellularity was influenced by inflammatory markers, while BMI mediated the association between UPF consumption and hypothalamic cellularity. Our findings indicate that UPF consumption is associated with poor metabolic health and neuroinflammation through adiposity and independent of it.

1:00

Food Insecurity: What Is It, Who Experiences It, And Why Is It So Strongly Associated With Health Outcomes?
Daniel Nettle
Institut Jean Nicod, Paris, France

Food insecurity—defined as limited or uncertain access to adequate and nutritious food—is surprisingly prevalent in affluent countries, and quite strongly associated with obesity, poor health, and premature mortality. What do these associations actually mean in causal terms? Someone is classified as experiencing food insecurity if they answer ‘yes’ to one or more items on a food-insecurity questionnaire. But the questions mention quite a lot of different things, notably being worried, not having enough money, and being hungry or not having enough to eat. Thus, food insecurity could mostly be picking up: psychiatric morbidity (anxiety); low income; inadequate nutrition; or some combination of all of these. We thus need to ask: under what circumstances do people answer ‘yes’ to food insecurity questions, and what do we know about the ingestive behaviour of people who do so? On the former question, food insecurity is a fairly direct consequence of a low income relative to household requirements. It is one of a series of deprivations that occur progressively as income diminishes and people become unable to secure increasingly basic needs. Being materially deprived in this way causes people to feel more anxious and depressed. On the latter question, the main differences seem to reside not in the overall amount of hunger or intake, or in dietary composition, but rather in the temporal variability of ingestion, especially from day to day. I will discuss implications for the epidemiological literature on food insecurity and health.

3:00

Why Do Humans Blend Macronutrients?
Annika N. Flynn¹, Peter J. Rogers¹, Mark Schatzker², Jeffrey M. Brunstrom¹
¹Nutrition and Behaviour Unit, School of Psychological Science, University of Bristol, Bristol, United Kingdom, ²McGill University, Montreal, QC, Canada

Foods with a more equal blend of energy from carbohydrate and fat are found to be more rewarding. Previously, we hypothesised that the underlying mechanism is reduced satiety – these ‘combo’ foods deliver less satiety per calorie (i.e., have a higher energy-to-satiety ratio). Thus, combo foods are more rewarding because they facilitate energy intake – the goal of eating is to ingest nutrients, not to achieve satiety. Consistent with this hypothesis, our work shows that combo foods are (1) more palatable, (2) more rewarding, and (3) less satiating. More recently, we have become interested in how energy-to-satiety ratio might influence everyday dietary behaviours and whether humans strategically combine foods to form a meal (e.g., cheeseburger and fries). Taken together, I will suggest that these real-world preferences and decisions can be interpreted through the lens of optimal foraging.

3:30

All Mixed Up: A Sensory Scientist&Rsquo;S View Of Food Formation And Eating Behavior.
John Hayes^1,2
¹Sensory Evaluation Center United States, ²Department of Food Science, College of Agricultural Sciences, The Pennsylvania State University, University Park, PA, United States

Discussions of formulation and eating behavior are implicitly mediated via sensation and affective responses. Dr. Hayes will review the putative causal chain linking formulation to intake in humans, including some logical fallacies and empirical data that challenge this common framework. Insights on cross modal interactions, mixture suppression, the bliss point, and individual differences will be discussed within the context of food reformulation.

4:00

Reinforcing Properties Of Hyper-Palatable Foods And Within-Meal Energy Intake
Tera Fazzino^1,2, Joseph Bellitti^1,2, Daiil Jun^1,2
¹Department of Psychology, University of Kansas, Lawrence, KS, United States, ²Cofrin Logan Center for Addiction Research and Treatment, University of Kansas, Lawrence, KS, United States

Rationale/premise: A definition of hyper-palatable foods (HPF) was developed in 2019 and specifies quantitative combinations of nutrients (fat and sodium; fat and sugar; carbohydrates and sodium) at thresholds not found in nature. The nutrient pairs in HPF are hypothesized to be a mechanism that yield acute rewarding effects during consumption, which can lead to overeating, and garner strong wanting and drive to consume HPF. Research using multiple methodologies has tested these hypotheses. Methods: Study 1 used an experimental paradigm with N=339 participants online to test the acute rewarding and behavioral reinforcing properties of HPF with elevated sodium, relative to matched foods without sodium (non-HPF). Study 2 used smartphone-based remote food photography methodology to assess the role of HPF in within meal energy intake among N=29 participants who reported 345 total eating occasions in free-living conditions. Results: Study 1: HPF were significantly more liked and more desired (wanted), relative to matched foods without sodium, with large effects (η² = .56-.68, p-values <.001). Participants were willing to pay more for HPF relative to matched items without sodium (η²=.17, p <.001), indicating HPF were more strongly valued as rewards. Study 2: Bayesian mixed models indicated that when participants consumed greater %kcal from HPF in eating occasions than their average, they consumed greater total kcal during the eating occasions (Median β = 0.09, pd = 99.56%), and post-meal endorsed greater eating despite feeling full (Median β = 0.15, pd = 96.45%), when accounting for hunger and energy density. Conclusions: HPF were liked and wanted more, and were valued more as rewards than matched foods without sodium (non-HPF), indicating their strong reinforcing properties and highlighting the role of sodium in their reinforcing effects. Findings from the free-living study identified the role of HPF themselves in within-meal energy intake, distinct from individual-level differences in HPF intake.

3:00

Reduced Subjective Valuation Of High-Caloric Density Foods After Bariatric Surgery: Associations With Appetite Regulating Hormones (New Investigator Travel Awardee)
Patrick Gagnon^1,2,3, Justine Daoust^1,2,3, Melissa Pelletier¹, Amelie Lachance^1,2,3, Yashar Zeighami⁴, Sylvain Iceta^1,5, Laurent Biertho⁶, Alain Dagher⁷, Andre Carpentier⁸, Andre Tchernof^1,2, Andreanne Michaud^1,2,3
¹Institut de cardiologie et de pneumologie de Quebec, Universite Laval, Quebec, QC, Canada, ²Ecole de nutrition, Universite Laval, Quebec, QC, Canada, ³Centre Nutrition, sante et societe (NUTRISS), Institut sur la Nutrition et les Aliments Fonctionnels, Quebec, QC, Canada, ⁴Douglas Research Center, McGill University, Montreal, QC, Canada, ⁵Departement de psychiatrie et de neurosciences, Universite Laval, Quebec, QC, Canada, ⁶Departement de chirurgie generale, Institut de cardiologie et de pneumologie de Quebec, Universite Laval, Quebec, QC, Canada, ⁷Montreal Neurological Institute, McGill University, Montreal, QC, Canada, ⁸Division endocrinologie, Departement de medecine, Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Universite de Sherbrooke, Sherbrooke, QC, Canada

Subjective valuation (SV) is a key brain process in which value is assigned to options based on perceived benefits. To our knowledge, no study has explored the effects of bariatric surgery on food SV or its associations with appetite-regulating hormones. We therefore aimed to investigate this, as measured by Willingness-to-Pay (WTP), for both high-caloric density foods (HCF) and low-caloric density foods (LCF). Sixty-one participants with severe obesity, scheduled for bariatric surgery (mean age=43.7±9.3 years; mean BMI=44.2±4.0 kg/m²) were included. WTP was assessed using the Becker-Degroot-Marschak food auction task during fMRI sessions conducted pre-surgery and at 4, 12, and 24 months post-surgery where participants had to bid between $0 and $5 on HCF or LCF. In each session, blood samples collected during fasted and postprandial states were analyzed for glucagon-like peptide 1 (GLP-1), peptide YY (PYY) and total ghrelin levels. Mixed-effect models showed a significant reduction in mean WTP for HCF post-surgery compared to pre-surgery (pre: $2.38±0.65; 4, 12, 24 months: $1.76±0.88, p<0.001; $2.07±0.76, p<0.001; $2.17±0.73, p=0.03, respectively). No significant changes were observed for LCF (p>0.05). WTP for HCF was positively associated with fasted total ghrelin (β=0.002, p<0.001) and negatively with postprandial PYY (β=-0.003, p=0.019). No significant association was found for GLP-1. These findings suggest that bariatric surgery reduces SV specifically for high-calorie foods, which is associated with changes in appetite-regulating hormones. Further fMRI analyses will explore how these variations manifest in brain activity, providing insights into food valuation mechanisms post-surgery.

3:15

Parental Feeding Practices Protect Children With Low Inhibitory Control From Excess Gains In Body Fat
Kyle Hallisky, Alaina L. Pearce, Kathleen L. Keller
The Pennsylvania State University, University Park, PA, United States

Deficits in inhibitory control (IC) are a risk factor for obesity. However, not all children with poor IC develop obesity, suggesting environmental factors, such as parental feeding practices, may mitigate risk. We tested whether parental monitoring and restriction of child feeding moderate the association between child IC and adiposity gain in middle childhood. A secondary data analysis was conducted from a longitudinal cohort of 77 children, ages 7 to 8, without obesity at baseline (T1). At T1, children completed computerized go/no-go (GNG) and food-specific stop-signal (SST) tasks measuring IC. Parents reported feeding practices with the Child Feeding Questionnaire. Adiposity (total body fat %) was assessed via Dual X-ray Absorptiometry at T1 and again at follow-up (T2), approximately 1 to 2.5 years later. Linear regression models, adjusting for child age, T1 adiposity, follow-up duration, and sex, found significant interactions for both GNG (p=0.04) and SST performance (p<0.01). In children with low parental monitoring, higher GNG % false alarms was associated with greater body fat % change (β=0.35, SE=0.15, p=0.02). SST stop signal reaction time interacted with parental restriction such that in children with high parental restriction, lower IC was associated with less body fat % change (β=-0.42, SE=0.19, p=0.03), but in children with low parental restriction, lower IC was associated with greater body fat % change (β=0.33, SE=0.18, p=0.08). These findings suggest feeding practices moderate the association between child IC and adiposity gain. In children with low parental monitoring and restriction, lower IC was associated with greater adiposity gain. Parental monitoring may be a promising strategy to reduce excess weight in children with low IC.

3:30

Multi-Dimensional Architecture-Based Personalized Digital Therapeutic: Development And Initial Clinical Validation For Eating Behavior Intervention In Obese Women
Seolha Lee¹, Juyoung Shin², Miyoun Choi³, Hyunhyung Kim², Jimin Choi⁴, Soomin Kim⁵, Yerin Park⁶, Seongmin Hwang², Taesung Lee¹, Saningun Lee³, Dong Jae Lee³, Hyung Jin Choi^1,2
¹Department of Biomedical Sciences, Seoul National University College of Medicine, seoul, Korea, ²Department of Brain and Cognitive Sciences, Seoul National University, seoul, Korea, ³Healthcare Research Institute, Drdiary, seoul, Korea, ⁴Department of Medicine, Korea University College of Medicine, seoul, Korea, ⁵Department of Medicine, Kyunghee University College of Medicine, seoul, Korea, ⁶Department of Biosystems and Biomedical Sciences, Korea University College of Health Science, seoul, Korea

Background: Obesity is a multifactorial condition influenced by metabolic, behavioral, and psychological factors. Traditional weight loss programs often overlook individual variations in eating behavior, cognitive distortions, and real-time metabolic responses. This study integrates three key components: (1) eating behavior-based tailored interventions addressing emotional eating, external eating, and food addiction, (2) cognitive behavioral therapy (CBT) targeting cognitive distortions prevalent in young women with obesity, such as perfectionism and impulsivity, and (3) continuous glucose monitoring (CGM)-guided personalized dietary management. Methods: A prospective, non-blinded randomized controlled trial was conducted with 105 overweight female participants (BMI ≥23). Participants were classified based on eating behavior tendencies and randomly assigned to an intervention group (n=70) receiving CGM-based personalized coaching with tailored CBT and eating behavior interventions, or a control group (n=35) receiving standard care, including general health education and lifestyle advice, without personalized digital coaching. Outcome measures included body composition, dietary intake, psychological assessments, and buffet test results at baseline, post-intervention, and 8-week follow-ups. Results: Following the digital intervention (DI), significant reductions were observed in emotional eating (p = .003), external eating (p = .041), and food addiction (p = .018) in the intervention group compared to the control group. In the buffet test, the intervention group showed a greater reduction in total carbohydrate intake (p = .002) and palatable food consumption in kcal (p <.001) compared to the control group, with significant between-group differences. Additionally, the proportion of healthy food choices increased more in the intervention group, with a significant between-group difference (p = .023). Regarding body composition, there was a trend toward greater reductions in both body weight and waist circumference in the intervention group (p <.1). Conclusion: This study advances the field of digital therapeutics by demonstrating the synergistic effects of CGM, behavioral profiling, and cognitive restructuring in obesity management, offering a scalable, personalized strategy for sustainable weight control.

3:45

Tirzepatide Dampens Food Motivation And Food Cue-Induced Nucleus Accumbens Dopamine ReleaseIn Rats
Serena X. Gao^1,2, Alexander Bashaw^1,2, Sophia L. Fischer¹, Olivia Moody¹, Nicolas Morano¹, Ann Law¹, Scott E. Kanoski¹, Tito Borner¹
¹Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, United States, ²Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, United States

Recent studies employing the GLP-1/GIP dual analog tirzepatide have shown enhanced weight loss and reduced malaise compared to GLP-1 receptor (GLP-1R) agonism alone. However, the neurobehavioral mechanisms mediating tirzepatide’s superior efficacy over GLP-1 monotherapy are poorly understood. Here, we investigated how tirzepatide influences appetitive motivational processes associated with highly palatable food. In adult male rats, we first confirmed GIPR mRNA expression in the mesolimbic system using fluorescent is situ hybridization. To assess the effect of tirzepatide on motivation for palatable food, rats were trained in an effort-based lever pressing task for high-fat/high-sugar pellets. When tested using a progressive ratio reinforcement schedule, we showed that systemic tirzepatide dose-dependently reduced lever presses and response break point, indicating decreased motivation to work for palatable food. Next, to explore the effects of tirzepatide on food cue-induced nucleus accumbens (ACB) dopamine (DA) signaling, we expressed D2R-based fluorescent sensors in the ACB of rats and measured DA binding during an auditory cue Pavlovian discrimination procedure in which one cue (CS+) signaled liquid sucrose reinforcement, whereas another cue (CS-) did not. Our results revealed that tirzepatide reduced ACB DA binding upon presentation of the CS+ but not the CS-, indicating an attenuation of food cue-associated dopamine release.These results were obtained in the absence of effects on latency to consume sucrose or amount consumed. Collectively, these findings suggest that tirzepatide modulates palatable food motivation by altering mesolimbic DA release, offering new insights underlying the enhanced efficacy of dual GLP-1R/GIPR agonism compared to mono GLP-1R agonism.

4:00

Semaglutide-Induced Conditioned Taste Aversion Suppresses Dopamine Signaling To Sucrose
Maxine Loh¹, Cesia Llort¹, Jordan Opoka¹, Mitchell Roitman^1,2
¹Department of Psychology, University of Illinois at Chicago, Chicago, IL, United States, ²Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, IL, United States

Glucagon-like peptide-1 receptor (GLP-1R) agonists (e.g., semaglutide) have been successfully developed to treat diabetes and obesity. However, semaglutide users experience gastrointestinal distress, nausea, and shifts in food preference. Preclinical work shows that GLP-1R agonists can induce a conditioned taste aversion (CTA) – a robust phenomenon where illness associated with initially palatable food promotes subsequent rejection. We have recently shown that phasic dopamine signaling to sucrose is suppressed after acquisition of a lithium chloride (LiCl)-driven CTA. Here, we tested the hypothesis that CTA formed through semaglutide-sucrose pairing will suppress sucrose-evoked phasic dopamine signaling. Dopamine (in vivo fiber photometry) and behavior (DeepLabCut) were recorded during sessions of intraoral 0.3M sucrose delivery. Initially sucrose-naïve rats received injection (i.p.) of either vehicle (Unpaired) or a malaise-inducing dose (10nmol/kg) of semaglutide after the first session (e.g. Conditioning). The following day, rats received the opposite injection in the home cage. This procedure was repeated weekly for 3 pairings. Daily sessions continued without injection (Extinction). While semaglutide caused similar decreases in body weight and temperature in Unpaired and Paired rats, only Paired rats exhibited behavioral evidence of a CTA. Likewise, phasic dopamine responses to sucrose were progressively suppressed with each Conditioning session only in Paired rats. These findings demonstrate that, akin to LiCl, GLP-1 agonism can cause plasticity within the mesolimbic system. Our work provides a platform on which the effects of satiety versus malaise circuits and/or pharmacological interventions against malaise for impact on dopamine signaling can be tested.

4:15

A Role For Glp-1R Positive Neurons In The Parasubthalamic Nucleus In Appetite Suppression
Jo Edward Lewis, Danae Nuzzaci, Mireia Montaner, Paula-Peace James-Okoro, Fiona Mary Gribble, Frank Reimann
Institute of Metabolic Science Metabolic Research Laboratories & MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom

GLP-1 receptor (GLP1R) and dual GLP-1/GIP receptor agonists are now widely used to treat diabetes and obesity, however, the physiological importance of different neuronal populations expressing these receptors is still not fully understood. Feeding behaviour is regulated by a network of neuronal populations in the brain and the parasubthalamic nucleus (PSTN), an incompletely understood brain region in the posterior hypothalamus, has been implicated in the regulation of food intake in response to other gut hormones (e.g. CCK and PYY). As mouse models expressing Cre under the control of the GIPR or GLP1R promoter report the PSTN, we sought to investigate the functional importance of these receptors in the PSTN using optogenetic, chemogenetic and viral tracing techniques. Administration of GLP1R or GIPR agonists increased cFOS staining in the PSTN. However, chemogenetic activation of Glp1r-, but not Gipr-expressing PSTN neurons reduced feeding, whilst neither had an effect on intraperitoneal glucose tolerance. We found that PPG (GLP-1 producing) neurons innervate the PSTN, suggesting a role for GLP-1 signalling in this nucleus. Optogenetic activation of PPG fibers in the PSTN also reduced feeding in ad lib fed animals, increasing latency to feeding initiation. Glp1r-expressing PSTN neurons were found to project to distinct brain regions implicated in the control of food intake, including the lateral parabrachial nucleus and the nucleus of the solitary tract. Our studies demonstrate that GLP1R-stimulation in the PSTN is relevant for the control of food intake, likely downstream to PPG neurons in the hindbrain, rather than peripheral GLP-1 signals, which are unlikely to reach this nucleus.

10:00

Simple Pleasures: Regulation Of Feeding And Social Interactions By The Lateral Hypothalamus
Anne Petzold, Rebecca Figge, Hanna van den Munkhof, Tatiana Korotkova
University of Cologne, Cologne, Germany

Animals have to coordinate and prioritize multiple, at times competing basic needs to ensure survival and reproduction. Nutritional needs, such as hunger and thirst, ought to be balanced and weighed against competing needs like mating. Despite a long-known crucial role of the lateral hypothalamus (LH) in the regulation of hunger and thirst, the neuronal mechanisms enabling representation and orchestration of multiple innate behaviours are not yet understood.Using deep-brain calciumimaging in freely behaving mice, optogenetics and chemogenetics, we investigated functions of two complementary neuronal populations in LH in feeding and social interaction. Despite hunger or thirst, leptin receptor-expressing LH neurons limit feeding and drinking while promoting social interaction, and encode conspecifics of opposite sex. Conversely, neurotensin-expressing LH neurons specifically prioritize drinking despite hunger, and reduce social interactions. Thus, both LH populations act in a complementary manner to enable the flexible fulfillment of multiple essential needs.

10:30

Threat Modulation Of Appetite: Hypothalamic Neuronal Mechanisms At Play
CELINE RIERA
Cedars-Sinai Medical Center

Despite extensive knowledge about integration of hormonal cues in the mediobasal hypothalamus (MBH) to control feeding and energy expenditure processes, the impact of sensory cues in this brain area has remained poorly understood. We have showed that cholecystokinin expressing neurons in the dorsomedial hypothalamus integrate olfactory cues associated with predator threats. We present new results characterizing the functional output of these neurons on feeding in health and obesity.

10:45

A Hypothalamic Circuit That Modulates Feeding And Parenting Behaviors
Michael J Krashes¹, Ivan C Alcantara^1,2
¹NIDDK/NIH, Bethesda, MD, United States, ²Brown University, Providence, RI, United States

Across mammalian species, new mothers undergo behavioral changes to nurture their offspring and meet the caloric demands of milk production. While many neural circuits underlying feeding and parenting behaviors are well characterized, it is unclear how these different circuits interact and adapt during lactation. Here, we characterized the transcriptomic changes in the arcuate nucleus (ARC) and the medial preoptic area (MPOA) of the mouse hypothalamus in response to lactation and hunger. Furthermore, we showed that heightened appetite in lactating mice was accompanied by increased activity of hunger-promoting agouti-related peptide (AgRP) neurons in the ARC. To assess the strength of hunger versus maternal drives, we designed a conflict assay where female mice chose between a food source or a chamber containing pups and nesting material. Although food-deprived lactating mothers prioritized parenting over feeding, hunger reduced the duration and disrupted the sequences of parenting behaviors in both lactating and virgin females. We discovered that ARC^AgRPneurons inhibit bombesin receptor subtype-3 (BRS3) neurons in the MPOA, a population that becomes more active postpartum and governs parenting and satiety. Selective activation of this ARC^AgRP to MPOA^BRS3circuit shifted behaviors from parenting to food-seeking. Thus, hypothalamic networks are modulated by physiological states and work antagonistically during the prioritization of competing motivated behaviors.

10:00

Hypothalamic Circuits Shape Accumbal Dopamine Release To Drive Feeding (Elsevier Physiology & Behavior New Investigator Travel Awardee)
Sam Z. Bacharach¹, Laryssa O. Coutinho¹, Katie A. Zappetti^1,2, Amber L. Alhadeff^1,2
¹Monell Chemical Senses Center, Philadelphia, PA, United States, ²University of Pennsylvania, Philadelphia, PA, United States

Agouti-related protein (AgRP)-expressing neurons in the Arcuate nucleus of the hypothalamus (Arc) are tuned to hunger state and critical for feeding behavior. Stimulation of AgRP neurons robustly drives food intake and increases nucleus accumbens (NAc) dopamine (DA) release to food. However, the neural mechanisms linking energy-sensing circuits to mesolimbic DA remain poorly understood. Here, we combined chemogenetic manipulations with in-vivo fiber photometry measurements of a DA sensor in mice (n=79) to test the hypothesis that AgRP neurons bidirectionally modulate DA release to food. We used ANOVA with post hoc t-tests to analyze data. Chemogenetic excitation of AgRP neurons increased NAc DA release to food presentation; conversely, inhibiting AgRP neurons under mild food restriction attenuated DA responses to food. DA release positively correlated with subsequent food intake, and pharmacological blockade of NAc DA receptors suppressed AgRP neuron-driven feeding. Further, these effects depended on olfaction, suggesting AgRP neurons drive food-seeking by enhancing DA responses to food-related olfactory cues. We next probed circuit mechanisms mediating this effect by optogenetically stimulating seven major Arc^AgRP projections while recording NAc DA (n=75 mice). Stimulation of Arc^AgRP projections to the BNST, LHA, PVH, or PVT, but not the CeA, PBN, or PAG, robustly increased food consumption, confirming previous reports. Stimulation of Arc^AgRP projections to the LHA, PVH, and PVT increased NAc DA when food was present, but not from axon stimulation alone. Ongoing studies investigate downstream neuronal populations linking Arc^AgRP neurons to NAc DA release. These findings support a functional role for AgRP neurons in modulating dopamine signaling to drive food intake.

10:15

Metabolic Signals Shape Learning And Decision-Making (New Investigator Travel Awardee)
Anne Kuehnel¹, Alica L Guzman², Sahiti Chebolu³, Melina Ghralow², Kristin Kaduk², Peter Dayan^3,6, Birgit Derntl^2,4, Nils B Kroemer^1,2,4,5
¹Section of Medical Psychology, Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany, ²Department of Psychiatry and Psychotherapy, Tübingen Center of Mental Health, University of Tübingen, Tübingen, Germany, ³Department of Computational Neuroscience, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, ⁴German Center for Mental Health (DZPG), Tübingen, Germany, ⁵German Center for Diabetes Research (DZD), Neuherberg, Germany, ⁶Department of Computer Science, Tübingen, Germany

To support long-term homeostasis, reward-related behavior is tuned according to the metabolic state of the body. Thus, altered metabolic signaling has emerged as a potential contributor to mental and metabolic disorders. However, despite evidence in animals, the influence of metabolic state over reward-related learning in humans is unproven. Moreover, the effect of differences in metabolic traits (e.g., insulin sensitivity) that may alter this relationship is not yet clear, although it may offer mechanistic insight into disorders. To close this gap, we collected observational and interventional data concerning metabolic scaling of reinforcement learning in a sample of 84 individuals with a wide range of BMI (18 – 36 kg/m²). First, participants completed up to 60 runs of our App, Influenca, assessing learning and value-based decision-making over 4 weeks. At the same time, we performed ecological momentary assessment of metabolic state and continuous monitoring of glucose levels (every 5 min) to differentiate ‘objective’ and self-reported metabolic state. Using Bayesian mixed-models, we find that average wins depended on the change in glucose levels over the previous 20 min (wins: 95%CI=[-0.69,-0.06]). Second, in an experimental session we manipulated metabolic state via a caloric load (milkshake) vs. water. This increased response times (p<.001) and affected learning depending on trait metabolic markers (p=0.019). We show that caloric intake can affect how we learn and decide. Crucially, metabolism plays an essential role in scaling reward-related signals according to energy intake. Ultimately, inter-individual difference in the integration of metabolic state related to differences in body composition and metabolic traits will provide insights into adaptive and maladaptive behavioral changes.

10:30

A Subset Of Pedunculopontine Nucleus Neurons Promote Food Reward
Nicholas K. Smith, James Bianchi, Ruoxi Wu, Albert, T Yeung, Michelle Awh, Sukya Williams, J. Nicholas Betley
Department of Biology, University of Pennsylvania, Philadelphia, PA, United States

The modern food environment is brimming with advertisements, packaging, and contexts that powerfully drive consumption. As we learn to associate these cues with the palatable and rewarding foods that they predict, the cues themselves gain motivating power over our eating decisions. However, the neural circuits that shape food cue learning are incompletely understood. We hypothesize that an excitatory input to the ventral tegmental area (VTA) mediates the communication of food reward information to dopamine neurons, enabling the associative learning that ascribes appetitive drive to food cues. In mice, we found that the pedunculopontine nucleus (PPN) has a strong connection to the VTA. These PPN neurons that project to the VTA exhibit a robust response to food. Via circuit specific inhibition, we find that this PPN projection is essential for the dopamine response to food reward. Endoscopic imaging identified a specific population of neurons that respond preferentially to food stimuli over other salient stimuli, suggesting the potential for a separable pathway for food reward through the PPN. Using a spatial transcriptomic analysis, we have begun to parse apart genetically and anatomically defined cell types within the PPN. These findings identify the PPN as a critical pathway for food reward to the dopamine system, allowing animals to link environmental stimuli with associated cues. Targeting this pathway could change the motivational impact of eating, limiting the impact of the cues that can lead to tempt unhealthy eating.

10:45

Amylin Receptor Signaling In The Laterodorsal Tegmental Nucleus (Ldtg) Controls Food Intake Through A Neurotensin Projection To The Ventral Tegmental Area (Vta)
Marcos J. Sanchez-Navarro, Carlie Zhang, Samantha Fortin, Halcyon Hu, Matthew R. Hayes
University of Pennsylvania, Philadelphia, PA, United States

Research on the role of amylin signaling in the control of energy balance has focused on brainstem and hypothalamic nuclei, leaving other calcitonin receptor (CTR) expressing nuclei such as the mesopontine laterodorsal tegmental nucleus (LDTg) largely understudied. Our lab has shown that LDTg amylin signaling reduces feeding and body weight, but the downstream targets of LDTg^CTR cells mediating these feeding effects remain unknown. Interestingly, the LDTg is known to produce the neuropeptide neurotensin (Nts) and activation of Nts receptors in the ventral tegmental area (VTA) reduces feeding and body weight. However, whether LDTg^CTRneuron activation reduces feeding via Nts release into the VTA has not been explored. Here, we use circuit tracing techniques to anatomically characterize LDTg^CTRneurons and show that a subpopulation of Nts producing LDTg^CTR neurons projects to the VTA. Our results also show that LDTg amylin increases VTA cFos activation, suggesting a potential mechanism via which LDTg amylin signaling influences energy balance. To test the functional role of this circuit, we used a dual AAV approach to induce a unilateral circuit specific (LDTg --> VTA) CTR-KD. Our results show that this manipulation is sufficient to attenuate the anorexigenic effects of peripherally-delivered salmon calcitonin, a CTR agonist. Lastly, we used the Calcr::cre mouse line to induce projection specific chemogenetic excitation of this LDTg^CTR --> VTA pathway and showed that this manipulation is sufficient to reduce food intake and body weight in male and female mice. Altogether, these findings anatomically and functionally characterize a new amylin signaling pathway, further establishing the LDTg as a potential target for novel amylin-based pharmacotherapies to treat obesity.

11:00

A Reward-Related Signature Of Sleeve Gastrectomy In The Ventral Striatum: A Proteomics Study
E Guerrero-Hreins¹, R Papaluca¹, NJ Caruana¹, DA Stroud^1,2,3, MP Menden^1,4, A Stefanidis⁵, BJ Oldfield^6,7, CJ Foldi^6,7, AJ Lawrence⁸, P Sumithran^9,10, RM Brown¹
¹Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Melbourne, Australia, ²Murdoch Children, Research Institute, Royal Children Hospital, Parkville, Melbourne, Australia, ³Victorian Clinical Genetics Services, Royal Children Hospital, Parkville, Melbourne, Australia, ⁴Institute of Computational Biology, Computational Health Center, Helmholtz, Munich, Germany, ⁵Deakin University, Burwood Campus, Geelong, Australia, ⁶Department of Physiology, Monash University, 26 Innovation Walk, Clayton, Melbourne, Australia, ⁷Biomedicine Discovery Institute, Monash University, 23 Innovation Walk, Clayton, Melbourne, Australia, ⁸Florey Institute of Neuroscience and Mental Health, Parkville, Melbourne, Australia, ⁹Department of Surgery, School of Translational Medicine, Monash University, Melbourne, Australia, ¹⁰Department of Endocrinology and Diabetes, Alfred Health, Melbourne, Australia

People seeking obesity treatment often display compulsive overeating of high-fat/high-sugar (HFHS) foods, which is associated with dysregulation of striatal pathways, and hinders weight loss. Bariatric surgery reduces motivation for HFHS foods, but the neural mechanisms remain unclear. This study used a mouse model of sleeve gastrectomy (SG) to investigate striatal proteomic changes after bariatric surgery and associated alterations in food motivation. Male and female C57BL/6 mice (n=88) were fed a HFHS diet before undergoing SG or sham surgery (SHAM). Post-surgery, taste preferences and operant motivation for palatable food were tested. SG mice exhibited reduced sweet preference and motivation for a palatable reward compared to SHAM. Untargeted bulk mass spectrometry of the ventral striatum (NAcc) identified 6,955 proteins, of which 681 were differentially expressed in SG vs SHAM. SG-enriched NAcc proteins were linked to glutamatergic synaptic plasticity including postsynaptic neurotransmitter receptor internalisation. Motivated behaviour positively correlated with glutamatergic and dopaminergic proteins - glutamate receptor delta-1 (GluD1) and catechol-O-methyl transferase (COMT) - and negatively correlated with glutamate receptor delta-2 (GluD2), monoamine oxidase A (MAO-A), and monoamine oxidase B (MAO-B). Our findings reveal, for the first time, satiety-independent reductions in cue-induced seeking behaviour towards palatable food and surgery-induced proteomic changes in the ventral striatum, suggesting synaptic plasticity and enhanced phasic dopamine release as central mechanisms underlying bariatric surgery’s effects on reward-related eating.

11:15

Divergent Patterns Of Dopamine Signaling Responses Between The Hippocampus And The Nucleus Accumbens In Response To Meal Consumption
Alexander G Bashaw^1,2, Lea Decarie-Spain¹, Logan Tierno-Lauer¹, Alicia Kao¹, Cindy Gu¹, Scott E Kanoski^1,2
¹Human and Evolutionary Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, United States, ²Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, United States

Dopamine (DA) is a neurotransmitter critically involved in food-related reinforcement learning. While DA signaling in reward-related brain regions such as the nucleus accumbens (ACB) has been widely investigated, far less is known about DA function in the hippocampus (HPC), a brain region known for its role in episodic memory and food intake control. Human PET scans have shown elevated DA binding in the HPC after meal consumption, yet HPC DA binding dynamics over the course of a meal remain unknown. Here, we compared dorsal HPC and ACB (shell) DA binding during meal consumption using in vivo fiber photometry recordings with DA receptor-based fluorescent sensors in adult male Sprague Dawley rats. Photometry recordings revealed differential activity between the HPC and ACB DA binding at meal onset, where DA signal either dynamically decreased (HPC) or increased (ACB) at the first bite of food. Additionally, HPC but not ACB DA binding gradually increased throughout the meal and was significantly elevated in the post-meal relative to the pre-meal state. To directly investigate the role of HPC DA signaling in meal-related episodic memory, another group of rats were implanted with a canula targeting the dorsal HPC. HPC infusion of a DA receptor type 2 (D2R) antagonist immediately following meal consumption impaired meal location memory and reduced latency to consume a subsequent meal, suggesting that HPC DA signaling serves to encode meal-related memories. Collective results identify HPC DA-D2R signaling as a candidate neurochemical mechanism through which nutrient consumption promotes meal-related episodic memory.

1:00

Playing With Food &Ndash; Cultivating Acceptance For Vegetables In Children Using Learning Theory.
Marion Hetherington
University of Leeds, LEEDS, United Kingdom

Dietary intakes in children are often low in fruits and vegetables. In the UK fewer than 18% of schoolchildren eat the recommended five-a-day portions of fruits and vegetables. Intake of vegetables is especially low, yet vegetable intake confers long term health benefits beyond those of fruit. To encourage vegetable intake in infants and young children, we have conducted a series of experiments to test the efficacy of repeated exposure on weighed intake of vegetables in young children (during complementary feeding; at snack time in pre-schoolers). Whilst familiarisation is effective in increasing acceptance of vegetables, especially in infancy, we have also tested the impact of experiential learning, including sensory play and exploration, on intake and willingness to try vegetables. In a recent, cluster-randomized controlled trial with two arms (control vs intervention) we tested the effect of sensory food education on willingness to try vegetables in school age children. The intervention did not have the expected effect, instead, contextual facilitation increased willingness to try new foods across both arms. A consistent finding across these studies is the importance of individual differences, the naturalness of the eating environment and the social context of food exposure on outcomes. Promoting intake of vegetables can be achieved in several ways, taking account of the characteristics of the child (including age), type of eating episode (meal vs snack) and social context.

1:00 - 3:00 PM	Boardroom
SSIB BOARD MEETING (INVITATION ONLY)

3:45 - 5:00 PM	L1
MARS Lecture 1 - Sadaf Farooqi, University of Cambridge

5:00 - 6:30 PM	South Mezzanine
Opening Reception & Exhibits

9:00 - 10:00 AM	North & South Mezzanines
Poster Session, Exhibits & Coffee Break

12:00 - 1:30 PM	L1
Oral Session 1: All the feels; interactions between stress, emotion and ingestion

12:00 - 1:30 PM	L2
Oral Session 2: Coming to your senses; olfaction and gustation in ingestion

3:00 - 4:30 PM	L2
Symposium 1: Exercise as a Modifier of Feeding

3:00 - 4:30 PM	L1
Oral Session 3: Oh to be young; early life food perception and eating

4:30 - 5:30 PM	North & South Mezzanines
Poster Session, Exhibits & Coffee Break

6:30 - 8:00 PM	Offsite - The King's Arms Oxford
New Investigator Event, organized by the New Investigator Advisory Committee

10:00 - 12:00 PM	L1
Presidential Symposium

1:30 - 3:00 PM	On Own
Lunch

10:00 - 11:30 AM	L1
Symposium 2: GLP-1R agonists: what can we learn from these drugs? (Sponsored by Novo Nordisk)

10:00 - 11:30 AM	L2
Oral Session 4: Know thyself; interoception and ingestion

11:30 - 11:45 AM	L1
Innovation through Collaboration - Novo Nordisk Partnership Models

11:45 - 12:55 PM	L2
Professional Development Event, organized by the New Investigator Advisory Committee

1:00 - 1:55 PM	L1
MARS Lecture 2 - John Glendinning, Barnard College

2:00 - 4:00 PM	L1
New Investigator Travel Award (NITA) Symposium

10:00 - 11:30 AM	L2
Symposium 3: What food systems can teach us about drug use and addiction

10:00 - 11:30 AM	L1
Oral Session 5: Hot topics in ingestion and nutrition

11:45 - 12:45 PM	L2
Meet the Scientist, organized by the New Investigator Advisory Committee

1:00 - 2:00 PM	L1
MARS Lecture 3 - Daniel Nettle, Institut Jean Nicod

2:00 - 3:00 PM	North & South Mezzanines
Poster Session, Exhibits & Coffee Break

3:00 - 4:30 PM	L2
Symposium 4: It is all in the blend: Effects of combining macronutrients on food intake and reward

3:00 - 4:30 PM	L1
Oral Session 6: Treatments & Interventions for Disregulated Ingestive Behaviors

10:00 - 11:30 AM	L2
Symposium 5: The Competition is On! Balancing ingestive and competing behaviors (Celebrating the 75th Anniversary of NIDDK)

10:00 - 11:30 AM	L1
Oral Session 7: Beyond Homeostasis; how reward and learning influence eating

1:00 - 2:00 PM	L1
MARS Lecture 4 - Marion Hetherington, University of Leeds

7:00 - 11:00 PM	Offsite - Museum of Natural History
AWARDS CEREMONY & CLOSING BANQUET (FULL REGISTRATION REQUIRED)