4:00

Energy Allostasis: Uncovering The Hidden Link Between Metabolic And Mental Health
Camilla L. Nord
MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom

To survive, our brain must accurately predict internal states, enabling flexible, prospective regulation of the body’s physiology, or ‘allostasis’: eating before starvation, drinking before dehydration. Wide-ranging studies report a disruption in allostatic mechanisms in mental health disorders, potentially driving clinical features such as appetite dysregulation in major depression as well as known epidemiological comorbidity between depression and poor metabolic health. I will discuss a series of cognitive-computational neuroscience experiments investigating the overlap between mental and metabolic health, including finding that depression and diabetes are both associated with disruptions in effort-based decision-making, and that mental and metabolic health is associated with changes in reinforcement learning. I will situate these cognitive mechanisms in a broader model of energy allostasis as a link between disruptions to metabolism and mental health.

10:00

Shaping The Next Generation: The Impact Of Barbara Rolls&Rsquo; Mentorship On The Field Of Ingestive Behavior
Paige Cunningham
Cornell University, Ithaca, NY, United States

Over a highly impactful career spanning decades, Barbara Rolls has left a giant footprint and proved to be a true luminary in the field of ingestive behavior. Beyond her own work, through her dedication to mentorship Barbara has and continues to shape the next generation of scientists. As her last graduate student, Barbara’s mentorship echoes throughout my work and career. Our mechanistic investigation of sensory-specific satiety and hedonic determinants of meal intake contributed to our discovery of switching (alternations between meal components) as a behavior that is significantly associated with food intake in adults and children. Our investigation of the combined effects of variety and portion size highlights the need to consider how properties of food known to influence consumption can work together to drive greater energy intake than either property alone. And together, we developed The Satiation Framework, which moves beyond a focus on physiological fullness to consider satiation as a series of dynamic processes that drive meal termination. This framework informs my multidisciplinary approach to understanding determinants of energy intake at meals. Overall, Barbara’s mentorship has influenced not only the research questions that I hope to pursue over the course of my career, but also the way I approach science as a whole – with rigor, with intentionality, and with consideration of real-world implications and how our work can meaningfully benefit human health. So, while I am Barbara’s last graduate student, I see this not as an end of an era but as a start of the next generation, still very much shaped by the remarkable mentorship of Barbara Rolls.

10:30

From (Controlled) Plate To Paradigm: Honoring A Pioneer Of Portion Size And Energy Density Research
Jennifer O. Fisher
Temple University, Philadelphia, PA, United States

This talk will reflect on the scientific contributions and legacy of Barbara J. Rolls, whose research established portion size and energy density as fundamental determinants of food and energy intake in both children and adults. Drawing on my experiences as a graduate student at Penn State, I will highlight the culture of inquiry and methodological rigor that Barbara fostered, which has shaped my approach to science, as well as that of many others under her tutelage. I will describe how her research on portion size and energy density has shaped key concepts about the regulation of intake and stimulated subsequent work in pediatric populations, including my own. Finally, I will discuss how this evidence has been translated into policy-relevant implications, underscoring the substantial public health impact of her contributions. Central to Barbara’s legacy is a commitment to conceptual clarity and rigorous methodology, reflected in the elegant design of her controlled feeding studies and her persistent effort to understand eating behavior from multiple perspectives. This influence endures not only in the body of evidence she produced, but also in the many investigators whose approaches to studying eating behavior remain grounded in her work.

11:00

High Volume, High Impact: The Barbara Rolls Effect
Alexandria B Hast
The Campbell's Company, Camden, NJ, United States

Dr. Barbara Rolls has dedicated her career to understanding the fundamental drivers of food intake, producing a body of work on energy density, portion size, and dietary composition that is among the most cited and applied in nutritional science. That scientific legacy extends well beyond publications; it has shaped the careers of an entire generation of researchers now working across academia, government, and industry. Graduate training in the Rolls laboratory is defined by intellectual rigor and careful experimental design. These core competencies translate directly into high-impact careers, including in the food industry, where evidence-based thinking, regulatory fluency, and the ability to connect nutrition science to consumer behavior are increasingly in demand. Effective mentorship develops scientists who can operate at the boundary between discovery and application; and, Barbara Rolls has exemplified this role for decades.

11:30

Translating Science To Improve Health: Using Research To Support Evidence-Based Public Health Nutrition Decision-Making
Julie Obbagy
USDA, Medfield, MA, United States

Barbara Rolls’ mentorship directly impacted my decision to pursue a career in the Federal government translating science to improve health. My career involves developing, advancing, and applying methods to conduct systematic reviews and other evidence synthesis projects that examine the complex interplay between diet and health. The values required of gold standard evidence synthesis processes - identification of high-priority research questions, scientific rigor and transparency, management of biases and conflicts of interest, diversity of expertise and collaboration, and effective science communication - are all values that were central to my training experience with Barbara Rolls. Systematic reviews that are high-quality and trustworthy are critical for end users who use their findings to make evidence-based decisions that have real-world public health impact. A recent systematic review that examined the relationship between portion size and energy intake will be described to demonstrate how research is used to support evidence-based public health nutrition decision-making - and to illustrate the strength of Barbara Rolls’ research program.

12:00

A Double-Blind Study Of Olfactory/Sniff Training With A Randomized Blank Control Group
Richard L. Doty¹, Crystal Wylie^1,3, Ronald Devere², Vince Grosso³, Shima Moein³, Marco Fornazieri⁴
¹University of Pennsylvania, Philadelphia, PA, United States, ²Taste and Smell Disorders Clinic, Austin, TX, United States, ³Sensonics International, Haddon Heights, NJ, United States, ⁴Universidade Estadual de Londrina, Londrina, Brazil

Objectives: Persons with smell loss reportedly benefit “olfactory training” (OT). However, most OT studies ignore drop-out rates, lack double-blinding, and do not employ randomly assigned contemporaneous control groups to account for expectation, practice effects, regression to the mean, and spontaneous improvement. We addressed these shortcomings in a double-blind multi-center study, labelling the research “sniff training” to facilitate compliance. Methods: Of 134 smell-deficient patients we contacted, 96 agreed to participate. 27% did not complete the 4-month-long training period, resulting in a final study group of 70. The patients were andomly assigned to three 10-stimulus exposure groups: unlabeled odorants; labeled odorants; and odorless blanks. The UPSIT® was administered before and after the training period; 35 also received a smell threshold test. General linear models, ê2, and other statistical analyses were employed. Results: Although 64% improved on the UPSIT®, with 26% experiencing clinically meaningful improvement (i.e., ≥4 points), the three odor exposure groups did not differ in terms of such improvement. A 6.2% improvement in UPSIT® scores occurred independent of exposure group (p=0.003). A trend in improved threshold scores independent of exposure group was also evident (p=0.078). Conclusion: We found in a double-blind placebo-controlled study that OT with a blank produced the same degree of improvement over a 4-month training period as OT with olfactory stimuli. Confirmation from other similarly designed studies is clearly needed.

12:15

Momentary Withdrawal Symptoms Predict Ultra-Processed Food Intake During Dietary Reduction
Erica LaFata
Oregon Research Institute, Springfield, OR, United States

Rationale: Ultra-processed foods (UPFs) may engage addiction-like processes that disrupt ingestive control, yet prospective evidence on withdrawal-driven eating dynamics is limited. Hypothesis: Reducing UPFs without caloric restriction will elicit withdrawal symptoms that predict momentary lapses in dietary control. Species: Humans Sample: Adults (N=18; 83.3% female; M_age=51.33; ecological momentary assessment (EMA) data available for n=17) Methods: Participants completed a 3-day baseline followed by 14 days of UPF reduction while maintaining caloric intake. EMA repeatedly measured withdrawal symptoms (modified ProWS; 7–49 range), urges, and UPF intake (M=47.1 surveys per participant over the study period). Multilevel models examined within-person predictors of subsequent intake. Results: Withdrawal symptoms were observed in the low-to-mid range (M=17.29), consistent with real-time assessment of acute dietary change. Higher withdrawal symptoms predicted increased likelihood of UPF intake at the next timepoint (ps<.01), particularly mood-related symptoms (irritability, anxiety, mood swings; ps<.001). Urges also predicted subsequent UPF intake (p<.01). UPF intake, in turn, predicted subsequent increases in withdrawal symptoms (p<.001), indicating a bidirectional process. UPF consumption occurred in 23.0% of EMA reports despite reduction instructions. Conclusions: Prospective, real-time data support the presence of withdrawal-like symptoms during UPF reduction and identify negative affect as a key mechanism linking withdrawal to intake. Findings extend prior retrospective work by demonstrating dynamic, within-person associations in daily life and suggest that targeting withdrawal may improve dietary adherence.

12:30

Screen Time Predicts Eating In The Absence Of Hunger In Preschoolers: Attentional Bias To Food As A Candidate Mechanism (Elsevier Appetite New Investigator Travel Awardee)
Yashaswini Rajendra Bhat¹, John Brand², Diane Gilbert-Diamond², Jennifer A. Emond¹
¹Dept of Biomedical Data Science, Geisel School of Medicine at Dartmouth College, Hanover, NH, United States, ²Deptof Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, NH, United States

Behavioral Susceptibility Theory states that appetitive traits interact with environment to shape eating behavior. Screen media is a dominant feature of young children’s environment. Food ad exposure increases children’s intake and is associated with weight status, but whether longer term habitual screen time predicts Eating in the Absence of Hunger (EAH) energy intake is unknown. Eye-tracking measures of food attentional bias are associated with weight in children but have not been examined as a mechanism linking screens to eating. We tested whether habitual screen time predicts EAH energy intake in preschoolers and whether attentional bias mediates this relationship. In 42 children (3–5 y), attentional bias to food vs. toy images was measured via eye-tracking and EAH was assessed via a standard protocol. Parents reported weekly screen time (hr/day) through self-reported survey. Five children did not consume anything during the EAH protocol and were excluded from the analysis. In a linear model adjusting for age, sex, BMI-z, and household income, screen time (M=1.8, SD=1.0 hr/day) predicted log-transformed EAH; at the sample mean, one additional hr/day was associated with 36 additional kcals (p=.028). Screen time was positively associated with first fixation bias (FF) to food (path a: β=0.39, p=.068), and FF with EAH controlling for screen time (path b: β=0.23, p=.24). The direct effect of screen time on EAH controlling for FF was marginally significant, accounting for 16% of the direct effect (c′: p=.057). All coefficients are standardized. Results held adjusting for measured physical activity. These findings identify habitual screen time as an early-life exposure correlated with hedonic eating, with attentional bias to cues as a candidate mechanism.

12:45

Food Parenting As A Predictor Of Child Energy Intake After An Experimentally Manipulated Restrictive Period
Muhammad Jamal Khan¹, Hannah E. Kolpack¹, Lori A. Hatzinger², Jennifer L. Temple^1,3, Katherine N. Balantekin^1,3
¹Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, United States, ²Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, United States, ³Center for Ingestive Behavior, University at Buffalo, Buffalo, NY, United States

Controlling food parenting is often associated with less favorable child eating outcomes, whereas positive food parenting is generally associated with more favorable child eating outcomes. The goal of this study was to see how parent-reported typical food parenting predicted child energy intake at a test meal following 2 weeks of experimentally manipulated parental restriction. At baseline, 91 parent-child dyads (8-11 years old; 53.8% male) had their height/weight measured, and the parent completed the Structure and Control in Parent Feeding questionnaire. Parents were then instructed to restrict their child’s access to a frequently consumed preferred snack food (chosen from 7 options) and similar foods for 2 weeks. After 2 weeks, the child was given a test meal that contained 25 foods (including their restricted food), and 3 drinks. Linear regression models were used to examine if aspects of controlling food parenting (restriction and pressure to eat) and positive food parenting (consistent feeding routine and limit exposure) predicted child’s total energy intake during the test meal, split by child weight status. In children with overweight/obesity, pressure to eat positively predicted energy intake (p=0.03). Whereas in children with healthy weight, limit exposure positively predicted energy intake (p=0.03). There were no other significant findings. These findings suggest that the impact of experimentally-manipulated restriction may differ based on the typical food parenting environment and the child’s weight status.

1:00

Worth The Work: Influence Of Relative Value And Relative Motivation On Sweet Vs. Fruit Intake And Bmi
Jose Jarquin, Olufisayo Atande-Ogunleye, Susan Carnell
Johns Hopkins University School of Medicine, Baltimore, MD, United States

Food intake and body weight are the cumulative result of choices between consuming less healthy, higher energy-density [ED] foods (e.g. sweets) or healthy, lower ED foods (e.g. fruits). Such food choices are influenced not only by how much an individual values the food (liking, wanting), but by the varied costs they are willing to incur to obtain it (motivation/effort). We investigated how relative value and motivation for sweets vs. fruits, assessed across a variety of cost types, were associated with habitual diet and BMI. We used data from n=487 17-23y olds (70%F, BMI 15-42.5) on the Food Motivation Battery [FMB], assessing willingness to i) exert low effort (finger taps), ii) exert high effort (jumping jacks), and iii) pay for, hypothetical delivery of a selected sweet and fruit that they liked and sometimes consumed. Individuals completed a screener assessing habitual diet, and reported height and weight. Using sweet-fruit difference scores, we found that: Individuals who valued sweets more were more willing to incur costs of multiple types to obtain them (taps: β=0.46; jumps: β=0.46; pay: β=0.34). Greater effort scores for sweets were associated with higher habitual sweet intake (taps: β=0.10; jumps: β=0.14). Greater willingness to pay for sweets was associated with higher BMI (β=0.13), most strongly for those who valued sweets more (value*pay β=0.10). A similar interaction was seen for taps (β=0.05, ns). Real-world food choices and BMI are influenced by not only value but the relative costs individuals are willing to incur to obtain less healthy vs. healthy foods. Understanding how individuals weigh value and costs for different foods could identify cognitive or behavioral intervention points to improve diet and metabolic health.

1:15

Are You A Healthy Eater? Using Brain Responses To Food Cues To Predict Motivation To Consume Healthy Foods
Trinity Cheng, Liuyi Chen, Susan Carnell
Johns Hopkins University School of Medicine, Baltimore, MD, United States

Motivation to consume healthy foods may better predict an individual’s obesity risk than the more universally high motivation to consume less healthy foods. To investigate the neural underpinnings of such motivation, we identified a “healthy eater” phenotype in n=77 adolescents (16.3±1.27y; 37M; BMIz=0.64±1.21), then tested whether brain food cue responses could classify individuals into that group. Principal component analysis [PCA] followed by K-means clustering was applied to wanting, liking, frequency and appetizing ratings for fruits and vegetables [F&V] and high energy-density [ED] foods, ad libitum buffet intake, and % empty calories and % fiber intake from ASA24. Two clusters emerged, representing “healthy” (n=23), and “less healthy” (n=23) eaters. The healthy group showed higher intake and wanting for F&V, and lower intake and other ratings for high-ED foods. We then ran one-vs-rest RandomForest models using fMRI responses to F&V and high-ED food (vs. non-food) images to classify individuals. Models showed best discrimination for both the healthy (AUC=0.79, accuracy=71.3%) and less healthy (AUC=0.82, accuracy=71.2%) groups when using the F&V contrast as input. Feature importance analyses indicated these predictions were driven by superior parietal lobule, posterior cingulate, and parietal operculum. Traditional voxel-wise linear regression analyses (p<.001, cluster p<0.05) revealed that healthy vs. less healthy eaters showed greater caudate and superior frontal gyrus responses to high-ED foods, and reduced cerebellum responses across both high-ED and F&V contrasts, with no clusters surviving FDR. Machine learning methods capturing distributed nonlinear brain responses to food cues provide novel insights into neural substrates underlying motivation to consume healthy foods.

12:00

Control Of Water Intake By Glp-1 Action In The Anteroventral Third Ventricle Region
Sydney A David¹, Johanna L Sirkin², Destiny J Brakey², Matthew J Paul¹, Derek Daniels^2,3
¹Department of Psychology, State University of New York at Buffalo, Buffalo, NY, United States, ²Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY, United States, ³Center for Ingestive Behavior Research, State University of New York at Buffalo, Buffalo, NY, United States

The mechanisms controlling fluid and food intakes are intertwined, making it challenging to separate the specific neural and hormonal pathways that control each behavior. For instance, glucagon-like peptide-1 (GLP-1) has a role in the suppression of both food and fluid intakes, without clarity about sites of overlap and nonoverlap. The vasopressin-deficient Brattleboro rat provides a unique model to study the thirst-specific elements of the GLP-1 system. Brattleboro rats are polydipsic, and hyper-responsive to the fluid intake suppression caused by GLP-1 receptor (GLP-1R) agonist treatment, but show a hypophagic response to the treatment that is indistinguishable from that observed in wildtype rats. To better understand the brain regions that differ between Brattleboro rats and their wildtype littermates, we examined Fos- and GLP-1R-immunoreactivity after dehydration with or without subsequent access to water. These analyses revealed several areas with main effects of water access or genotype, but the anteroventral third ventricle (AV3V) region had an interaction effect in both the number of Fos-positive cells and the density of GLP-1R-immunoreactivity. We therefore hypothesized that GLP-1 selectively regulates drinking through specific neural circuits converging on the AV3V, rather than through broad activation of feeding-related pathways. In support of this hypothesis, we found that direct administration of the GLP-1R agonist Exendin-4 into the AV3V robustly reduced drinking without affecting feeding. We also observed a selective suppression of drinking when we chemogenetically excited AV3V-projecting neurons in the caudal brainstem. These findings are consistent with the model that GLP-1-related signals from the hindbrain converge on the AV3V to suppress thirst.

12:15

A Psychobioecological Intervention To Address The Food-Insecurity-Obesity Paradox
Nicholas V. Neuwald , McKenna E. Nicholls, Sarah E. Naula, Jennifer L. Temple, Leonard H. Epstein
University at Buffalo, Buffalo, NY, United States

Our lab has proposed a psychobioecological model theorizing food insecurity leads to metabolic and psychological adaptations favoring fat storage and increased preference for energy-dense food. Based on this model, we hypothesized that targeting these adaptations through a metabolically tailored diet and by reducing meal unpredictability would attenuate the mechanisms linking food insecurity with obesity risk. Twelve women (BMI 40.4 ± 8.1) with food insecurity and obesity participated in a 2-month stepped-wedge pilot intervention followed by a 2-month follow-up period, combining meal deliveries and behavioral coaching. Participants received 2-3 ready-to-eat meals per day for 4 nonconsecutive weeks, targeting a 20% daily calorie deficit and follow a high-protein (>30%), low-carbohydrate (<40%), low-glycemic-load diet. Weekly behavioral coaching and biweekly metabolic assessments informed individualized meal tailoring. The study is ongoing, with 5 participants having completed the protocol. Among these participants, mean weight loss was 7.5 ± 4.8 lbs. at post-treatment and 10.8 ± 4.0 lbs. at follow-up. The thermic effect of food increased from 2.9% at baseline to 4.6% post-treatment (+59%) and 9.0% at follow-up (+210.3%). Delay discounting decreased by 24.0% at post-treatment and 12.9% at follow-up relative to baseline. Relative reinforcing efficacy for high-energy-dense food declined 59.0% at post-treatment and 78.1% at follow-up, while perceived stress declined 6.7% and 24.7%, respectively. Preliminary findings suggest this treatment led to sustained behavioral and metabolic improvements which provide support for the psychobioecological model as a framework for addressing the food-insecurity-obesity paradox. Complete data will be available prior to the conference.

12:30

The Effect Of Medial Prefrontal Cortex Deep Rtms On Food Cravings And Body Weight In Adults With Obesity And Food Addiction: A Randomized Sham-Controlled Trial.
Roni Aviram-Friedman¹, Nimrod Agmon², Alexandra Panurov², Uri Alyagon², Abraham Zangen²
¹Department of Nutrition Sciences, Faculty of Health Sciences, Ariel University, Ariel, Israel, ²Department of Life Sciences and the Zelman Center for Neuroscience, Ben-Gurion University, Beer Sheva , Israel

The effect of medial prefrontal cortex deep rTMS on food cravings and body weight in adults with obesity and food addiction: A randomized sham-controlled trial. Rationale: Food addiction in obesity (FAOB) involves heightened cue-reactivity and intense cravings for palatable foods and shares neurobiological features with substance addiction. Deep rTMS targeting the mPFC/ACC reduced alcohol cravings and use in alcohol use disorder, suggesting potential to reduce food cravings and body weight in FAOB. Hypothesis: mPFC-targeted deep rTMS (H7 coil) will reduce food cravings and body weight in adults with FAOB. Species: Humans. Subjects: N = 28 adults with obesity (BMI 30–40) and food addiction. Procedures: Randomized, double-blind, sham-controlled trial. Participants received 15 active or sham dTMS sessions over 3 weeks, followed by a 30-day follow-up with behavioral nutrition support. Assessments at baseline, post-treatment (T15), and follow-up (FU) included Food-Stroop with EEG (N40, LPPa, LPPb), TFEQ, VAS satiety ratings, and body weight. Outcomes were analyzed with linear mixed-effects models. Results: Body weight did not change in either group. However, active treatment acutely reduced Food-Stroop bias (p <0.05) and modulated ERP components. At FU, the treatment group showed higher satiety (p = 0.01), lower cognitive restraint (p = 0.01), and reduced N40 and LPPb amplitudes vs. sham. Conclusions: Although body weight was unaffected, mPFC deep rTMS reduced neural and behavioral indices of food cravings and emotional reactivity to food cues in FAOB. Effects emerged mainly during follow-up, suggesting that combining neuromodulation with behavioral nutrition support may advance outcomes. These findings offer new insights into the neural mechanisms underlying food addiction and craving regulation in obesity.

12:45

Discovering Prokineticin Receptor 2 Agonists For The Treatment Of Obesity (New Investigator Travel Awardee)
Kate R. Bowman^1,2,3, Ayushi Mittal^1,2,3, Paul Buscaglia^2,3, Julien A. Sebag^2,3,4
¹Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, United States, ²Department of Pharmacology, University of Michigan, Ann Arbor, MI, United States, ³Caswell Diabetes Institute, University of Michigan, Ann Arbor, MI, United States, ⁴Life Sciences Institute, University of Michigan, Ann Arbor, MI, United States

While the rate of obesity is rising, safe and effective weight-loss medications are limited. GLP1R agonists promote weight loss but their use is accompanied by side effects (nausea, gastrointestinal discomfort, loss of muscle mass). It is therefore urgent to find new therapeutic targets for obesity. Prokineticin 2 (PK2) is an anorexigenic neuropeptide that activates two GPCRs, prokineticin receptors 1 and 2 (PKR1 and 2). PKRs are expressed in multiple brain regions and ICV administration of their agonist PK2 reduces food intake and body weight in diet-induced obese mice (n=5-8). PK2 retains its anorexigenic effect in PKR1 KO mice, identifying PKR2 as the mediator of the anorexigenic response (n=18-28). Silencing of PKR2 in amygdala neurons, but not arcuate nucleus neurons, abrogates the anorexigenic effect of PK2 (n=5-6), establishing amygdala PKR2 neurons as required for the inhibition of food intake by PK2. Importantly, unlike GLP1R agonists, we found that PK2 does not induce nausea or aversion. Because PK2 is not tractable as a drug, we developed a high-throughput screening assay to identify small molecule PKR2 agonists and screened 85,000 drug-like compounds. Hits were counter-screened against other GPCRs and PKR1 to eliminate non-specific compounds. Lead compounds with specific agonism for PKR2 were further characterized pharmacologically and tested for in vivo efficacy. ICV injection of compounds in mice resulted in significant inhibition of food intake and bodyweight (n=6-9), thus confirming that small molecule PKR2 agonists are promising candidates for the development of new weight loss drugs. Future work will involve chemical optimization of identified compounds to improve potency, efficacy and bioavailability.

1:00

Pre-Meal Olfactory Nudging Vs. Habituation: Feasibility Randomized Controlled Trial In Women With Overweight/Obesity
Surabhi Bhutani¹, Yao Zhao ^2,3, Emma Johnson¹, Victoria Esparza^1,2, Valentina Parma^2,3
¹San Diego State University, San Diego, CA, United States, ²Monell Chemical Senses Center, Philadelphia, PA, United States, ³University of Pennsylvania, Philadelphia, PA, United States

Although olfaction influences food choice, odor-based behavioral strategies are understudied in weight-management research. We hypothesized that brief pre-meal olfactory interventions would be feasible/acceptable in women with overweight/obesity and yield short-term changes in olfactory awareness, cravings, and diet outcomes. In a 2-week pilot RCT feasibility trial (N=45F; age 18-55 years; 60% white), participants were randomized to olfactory nudging (ON; brief exposure to “healthy” banana/strawberry fruit odors), olfactory habituation (OH; 10-min exposure to “unhealthy” banana pudding/strawberry cake odors), or control (10-min no-odor exposure) interventions. Baseline BMI and smell identification did not differ by group. ON was rated as more liked/accepted than OH and control (overall p=0.006; pairwise p=0.04 and p=0.007). Post-intervention, olfactory awareness showed a non significant increase in OH (Δ=+2.0±8.4) vs. ON (Δ=-2.1±5.0) and control (Δ=-1.7±8.9). Although total craving scores did not change, adjusted analyses showed that higher baseline autonomous motivation (control: 5.2±1.1 vs. ON: 6.1±0.9 and OH: 6.1±0.7; p=0.02) predicted lower carbohydrate craving at 2 week (b=-5.42, p=0.04). Salt craving decreased marginally across groups (p=0.06). Weight change did not differ across groups. Exploratory dietary patterns were mixed, with directional shifts in OH (lower protein and %protein, higher %carbohydrate) and ON (lower %fat). Our preliminary findings suggest that brief olfactory interventions are feasible and acceptable, particularly ON, and may yield short-term exploratory diet-related signals. More in-depth adjusted and longitudinal analyses will clarify relevance for ingestive behavior.

1:15

Effects Of A Restaurant-Based Intervention On Children&Rsquo;S Meal Selection: A Cluster-Randomized Trial
Stephanie Anzman-Frasca^1,2, Juliana Goldsmith¹, Mackenzie Ferrante³, Leonard Epstein^1,2, April Gampp⁴, Jess Haines⁵, Lucia Leone^2,6, Emily McCray¹, Rocco Paluch¹, Sara Tauriello¹
¹Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States, ²Center for Ingestive Behavior Research, Buffalo, NY, United States, ³School of Environmental and Biological Sciences, Rutgers University, New Brunswick, NJ, United States, ⁴Independent Health Foundation, Buffalo, NY, United States, ⁵College of Social and Applied Human Sciences, University of Guelph, Guelph, ON, Canada, ⁶School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, United States

Rationale. Restaurants are regular eating contexts for families, but most children’s meals at restaurants do not meet nutritional recommendations. Regular exposure to nutritious options may promote their acceptance. We tested effects of an intervention designed to promote healthier meal selection among children in restaurants. Methods. Six locations of a quick-service restaurant were randomized to intervention or control. Families with 4-to-8-year-old children (n=236) were randomized based on enrollment location and asked to complete 7 restaurant visits after baseline: 6 during a 2-month intervention period and a post-test visit. Intervention components included placemats promoting 2 healthier kids’ meals, the opportunity to select a toy instead of dessert, and a frequent diner card redeemable for a free kids’ meal after ordering a promoted meal 6 times. The primary outcome was whether a promoted meal was ordered at post-test, tested via Fisher’s test. Other outcomes were calories, saturated fat, sodium, and sugar ordered. Results. The intervention did not affect ordering of promoted bundled meals at post-test, although there were group differences in uptake of individual promoted items (p<.05; 28.4% of intervention group ordered a promoted item vs. 19.5% of controls). The intervention decreased calories, saturated fat, and sodium ordered for children during the study (p<.05, p<.01, and p<.01), with no effect on sugar. Yet there were no significant differences in nutritional characteristics of orders by post-test (e.g., 962.6 vs. 1033.5 calories ordered in intervention vs. control group; p=.07). Conclusion. Results show potential for these strategies to promote healthier orders, but effects dissipated over time, suggesting additional efforts are needed for sustainable impacts.

3:00

Fgf21 Signals Through Hindbrain Neurons To Alter Food Intake And Energy Expenditure During Dietary Protein Restriction
Redin A. Spann, Sora Q. Kim, Md Shahjalal Khan, Diana A. Albarado, Sun O. Fernandez-Kim, Hans-Rudolf Berthoud, David H. McDougal, Heike Muenzberg, Yanlin He, Sangho Yu, Christopher D. Morrison
Pennington Biomedical Research Center, Baton Rouge, LA, United States

Animals detect and respond to variations in nutrient availability, including reductions in dietary protein availability. Our work has established that the liver-derived metabolic hormone FGF21 is critical for adaptive responses to dietary protein restriction, and that it acts directly within the brain to mediate these effects. However, the precise neural circuit mediating these effects remains undefined. Here, we demonstrate that a discrete population of glutamatergic, Klb-expressing neurons in the nucleus of the solitary tract (NTS) mediates FGF21 action during protein restriction. Using a Klb-Flp mouse line combined with intersectional genetics, we show that NTS-KLB neurons are directly activated by FGF21. Systematic evaluation of previously implicated regions (SCN, PVN, VMH) reveals these areas are not required for FGF21-mediated responses to protein restriction. In contrast, selective ablation of NTS-KLB neurons prevents metabolic adaptations to protein restriction, including changes in food intake, food choice, and energy expenditure, while their chemogenetic activation is sufficient to drive these responses. These findings establish that NTS-KLB neurons directly respond to FGF21 and coordinate adaptive changes during protein restriction, identifying the neural circuit linking dietary protein sensing to metabolic adaptation.

3:30

To Be Announced
ANDREW WANG

4:00

Acute Prefrontal Cortex Response (By Functional Near Infra-Red Spectroscopy, Fnirs) To Ingestion Of Protein And Protein Preloads In Humans: Effects On Satiation Efficacy Rate And Subsequent Acute Intake Of Ultra-Processed Food.
Jennifer A Nasser
Drexel University, Philadelphia, PA, United States

Protein is accepted as the most satiating of all macronutrients as well as the macronutrient promoting the greatest satiety interval. Of current relevance to the US diet is the low level of protein per serving (~2 grams or less/100 kcal serving) contained in most ultra-processed foods (UPF), which make up close to 70% of daily caloric intake. This sparked my interest in the potential for proteins to promote satiation if protein ingestion occurred in close proximity to ingestion of UPF. Additionally, I have had an interest in examining the acute effect of protein ingestion on the prefrontal cortex (PFC) response in adult humans under satiating conditions to probe for potential mechanisms of satiation promotion. For this symposium I will present data from studies of protein ingestion as well as protein preload ingestion effects on subsequent acute intake of UPF with respect to regional activation in the PFC (assess by functional near infra-red spectroscopy, fNIRS) and describe a complementary study of protein ingestion effects in rodents assessed under a common protocol used in our human studies as a means of demonstrating causative mechanisms of satiation promotion. The main working hypothesis that underscores all of the protein-based studies is that acute food intake is less when dorsolateral PFC activation prior to, or during the eating episode is greater than dorsomedial PFC activation. Data accumulated in the human studies and complementary animal study is supportive of this hypothesis.

3:00

Early Ingestive Experience With A High-Fat Diet Alters The Developmental Trajectory Of Vagal Satiation Signaling And Produces Enduring Changes In Appetitive Behavior
Meaghan E. McCoy^1,2, Ciorana Roman-Ortiz², Jason Perez¹, Lindsey A. Schier², Anna K. Kamitakahara^1,3
¹Children's Hospital Los Angeles, Los Angeles, CA, United States, ²University of Southern California, Los Angeles, CA, United States, ³Keck School of Medicine of University of Southern California, Los Angeles, CA, United States

Early-life exposure to energy-dense, high-fat foods is increasingly common, yet how early dietary experience shapes the functional establishment of vagal sensory circuits, the primary pathway through which the gut conveys nutrient information to the brain, remains poorly understood. We hypothesized that early-life high-fat diet (HFD) exposure would alter vagally mediated satiation and appetitive behaviors. Litters of C57BL/6J mice were reared on chow (control) or HFD (HFD^EARLY) from birth until weaning (postnatal day [P]0–21), after which all offspring were maintained on chow. Behavioral cohorts (n=8–12/sex/group) were fasted overnight, injected with cholecystokinin (CCK), and presented with HFD at different ages to assess satiation. In control mice, robust CCK-dependent feeding inhibition emerged by P45 and persisted into adulthood. In contrast, HFD^EARLY mice displayed consistent, adult-like CCK-dependent inhibition at P35, indicating accelerated maturation of satiation signaling. Although adult satiation responses were similar between groups, durable changes in appetitive reward behaviors were revealed by 2-bottle preference and lick microstructure assays: HFD^EARLY females consumed more lipid and exhibited enhanced early-phase lipid licking, consistent with amplified appetitive responding. RNA sequencing of P21 nodose ganglia (n=7–8/group) identified 176 differentially expressed genes in HFD^EARLY mice, including genes associated with neuronal excitability and synaptic organization, suggesting candidate mechanisms through which early-life diet alters vagal sensitivity. These findings demonstrate that early-life dietary fat alters the developmental trajectory of vagal circuits and produces enduring, nutrient- and sex-specific changes in ingestive behavior.

3:15

Inflexible Thinking, Inflexible Eating: Poorer Executive Functioning Is Positively Associated With Food Fussiness During Early And Middle Childhood.
Rachel Fan, Kyle Hallisky, Kathleen L. Keller
The Pennsylvania State University, University Park, PA, United States

Picky eating in childhood is common, but extreme pickiness can lead to nutrient deficiencies, making it crucial for treatment to identify underlying cognitive processes. Executive functioning (EF) deficits could be associated with picky eating, which may partly stem from an inability to generalize foods across categories due to deficits in cognitive flexibility (a component of EF). Thus, we investigated whether poorer EF was associated with greater picky eating during early (ages 4-6y) and middle (ages 7-9y) childhood. Age was tested as a moderator, hypothesizing that the relationship would weaken with age due to a general improvement in EF and reduction of picky eating. A secondary data analysis from two multi-visit cohort studies (n=136; F=66) was conducted. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF2) for assessment of child EF (higher scores = worse EF) and the Child Eating Behavior Questionnaire Food Fussiness (FF) subscale for assessment of picky eating (higher scores = greater FF). Linear regression models (adjusted for parent income and education, child sex and BMI percentile (3.9-99.7), and study) found that poorer general EF was associated with greater FF (β=.35, p<.001). When considering the BRIEF2 subscales, the relationship with greater FF persisted for poorer behavioral regulation (β=.31, p<.001), emotional regulation (β=.24, p=.006), and cognitive regulation (β=.33, p<.001). Worse shifting abilities, or cognitive inflexibility, were also associated with greater FF (β=.28, p=.002). The relationship between EF and FF did not vary by child age (p=.71). These results suggest that EF could be a potential mechanistic process that contributes to picky eating across childhood, helping elucidate viable intervention targets.

3:30

Variety-Seeking When Eating In The Absence Of Hunger As An Obesogenic Eating Behavior In Children
John W. Long, Barbara J. Rolls, Kathleen L. Keller
Pennsylvania State University, University Park, PA, United States

Modern environments are characterized by abundant food variety but the extent to which children’s response to such variety presents a risk for overconsumption and obesity is unclear. We examined whether trying a greater number of foods while eating in the absence of hunger (EAH) was associated with children’s energy intake and adiposity, and whether these relations differed by appetitive traits. Children aged 7–9 without obesity completed a year-long study with EAH and body composition measured at baseline (T1; n=100) and follow-up (T2; n=80). At each visit, children consumed a standard meal to satiation followed 15 min later by 9 energy-dense foods (2.2–5.7 kcal/g) to assess EAH. Parents reported children’s appetitive traits via the Children’s Eating Behavior Questionnaire. Using pooled data across visits, linear mixed models examined whether number of foods tried (>2g eaten) predicted EAH energy intake and adiposity, and whether these relations were moderated by appetitive traits. Models were adjusted for visit number, sex, age, puberty, education, income, and maternal obesity. Across visits, foods tried predicted EAH energy intake, with each food tried corresponding to an additional 54.6 ± 5.5 kcal consumed (p<0.0001). Trying more foods was also associated with higher adiposity, including visceral adipose tissue and fat mass index (all p<0.05). Food and satiety responsiveness moderated associations between foods tried and EAH intake (FR: β = 17.7; SR: β = −28.7; both p<0.01) and visceral adipose tissue (FR: β = 4.3; SR: β = −6.3; both p<0.05). These findings suggest variety-seeking behaviors in food-rich environments contribute to obesogenic eating, particularly among children with greater food responsiveness and weaker satiety responsiveness.

3:45

Exposure And Access Drive Intake: A School-Based Produce Intervention Increases Fruit Consumption (Supported By The Ssib International Foundational Fund Given In Memory Of Drs. Jacques Le Magnen (France), Anton Steffens (The Netherlands), Jacob Steiner (Israel), Steven Cooper (The United Kingdom))
Smadar Hod-Ovadia^1,2, Moran Kilzi^1,2, Mona Boaz¹, Vered Kaufman-Shriqui^1,3
¹Department of Nutrition Sciences, Faculty of Health Sciences, Ariel University, Ariel, Israel, ²Leket Israel, Ra'anana, Israel, ³The Center for Urban Health Solutions (C-UHS), St., Michael's Hospital, Toronto, ON, Canada

Rational: Low fruit and vegetable intake is associated with increased chronic disease risk, particularly among low socioeconomic status (SES) populations due to cost and access barriers. School-based food distribution programs may provide a non-stigmatizing mechanism to improve dietary behaviors among families. Hypothesis: A combined intervention of rescued produce distribution and nutrition education will improve parental fruit and vegetable consumption. Species: Humans (parents of elementary school children) Number of subjects: 196participants Procedures (methods and statistical analyses): A 7-month cluster-controlled study in three schools assigned parents to: produce plus education (n=80), produce only (n=66), or control (n=50). Pre- and post-online questionnaires assessed diet and food security. Group differences were tested statistically, and logistic regression examined associations between the number of packages and improved consumption. Results: At baseline, 78% of parents consumed fewer than the recommended amounts of fruit and vegetables. Fruit consumption improved significantly in the intervention groups compared with the control group (p=0.028). Among households with worsening food security (8.7% to 14.3%), the combined intervention showed a protective effect on fruit intake (p=0.007). Each additional package increased the likelihood of improved fruit consumption by 6.7% (OR=1.067, 95% CI 1.003–1.135, p=0.04). Conclusions: School-based distribution of rescued produce, especially with nutrition education, improves parental fruit intake and may mitigate worsening food insecurity. This scalable, dignity-preserving model integrates food banks and schools to reduce nutritional disparities during rising food costs.

4:00

Food And Game-Time Delay Discounting: Associations With Appetite And Weight In Middle Childhood
Wenxuan Fan¹, Rosa Cano Lorente², Daphne Koinis-Mitchell², Viren D'Sa², Keri Rosch¹, Susan Carnell¹
¹Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Brown University, Providence, RI, United States

Appetitive traits such as food responsiveness [FR] are associated with child weight. Cognitive traits such as delay discounting [DD] – preference for a smaller sooner vs. larger later reward – are also associated with weight, but findings vary with reward type and age. To test an overarching hypothesis that FR and DD play complementary roles in food intake and weight, we assessed in RESONATE (a sub-study of RESONANCE) parent-report FR in 61 7-13y olds (61%M, BMIz 0.39+1.20), along with two experiential measures of DD with high salience in children: a food DD task (5 trials requiring choices between a smaller immediate vs. larger delayed candy reward), and a novel game-time DD task (9 trials requiring choices between shorter immediate vs. longer delayed game access). Children then underwent a post-meal eating in the absence hunger [EAH] test including fruit as well as snacks. Children chose the larger, delayed food reward on 4.08+1.07 trials, and the longer, delayed game access on 58.6+31.0% of trials. EAH intake was 152+131kcal (116+120kcal snacks, 36+50kcal fruit). FR was associated with food DD (r=0.27, p=0.041), but not game DD. Food and game DD were correlated (r=0.29, p=0.024). FR (but not food or game DD) was associated with child BMIz (r=0.29, p=0.026). FR was also associated with greater intake of snacks as a proportion of total intake but only in older children (FR*age p=0.049). Our findings demonstrate that parent-report FR and food DD, and measures of DD in relation to food and game-time, are related within individuals, but in middle childhood only parent-report FR predicts food intake and weight. Future RESONANCE analyses will combine brain and behavior data to test how appetitive and cognitive traits interact to influence intake and weight through development.

4:15

Maternal Prebiotic Supplementation Shapes Offspring Gut Microbiome And Improves Gut-Brain Axis Communication Into Adulthood
Jennifer M. Houston¹, Jillian M. Allen², Julia C. Cook¹, 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

Gut-innervating vagal afferents terminate in the nucleus of the solitary tract (NTS), conveying post-ingestive cues to regulate meal size. Maternal obesity increases risk of metabolic disorders in offspring. Rat pups born to high fat (HF)-fed dams show reduced sensitivity to gut satiety peptides and reduced post-prandial NTS activation associated with increased meal size. HF diet-driven microbiota changes are necessary and sufficient to disrupt gut-brain communication. We hypothesized improving HF-fed dams’ microbiota would improve offspring gut-brain signaling. Sprague-Dawley dams were fed a chow, HF, or HF+12% resistant starch (RS) diet during pregnancy and lactation. Chow and HFRS dam microbiome profiles did not significantly differ. At post-natal day 10 (P10), HF offspring were enriched in pro-inflammatory Bacteroidaceae compared to chow offspring. HFRS pups were enriched in Bifidobacteriaceae, associated with leanness. HF pups displayed reduced IB4+ and increased Iba1+ staining at the NTS (p<0.05), indicating inflammation-driven vagal withdrawal. Despite chow weaning, gut-brain axis inflammation persisted in adult HF offspring (p<0.01). Adult HF offspring showed reduced CART activation and increased Iba1+ staining in the nodose ganglion, indicating chronic inflammation and altered post-ingestive signaling (p<0.05). HF offspring had increased meal size and failed to reduce intake in response to cholecystokinin (CCK, 1.5μg/mL/kg). Maternal supplementation prevented gut-brain axis inflammation and altered vagal signaling, evidenced by reduced Iba1 and restored CART activation post-ingestion. Maternal HF diet increases pro-inflammatory microbiota and alters vagal structure and function. Maternal RS supplementation can improve gut-brain communication into adulthood.

10:00

Monoamine Release Dynamics In The Human Amygdala Dissociate Components Of Food Reward
Matt Howe^1,2, Seth Batten¹, Leonardo Barbosa¹, Monica Ahrens³, Terry Lohrenz¹, Jason White¹, Robert Bina⁴, Mark Witcher^1,5, Read Montague^1,6, Alexandra DiFeliceantonio^1,7
¹Fralin Biomedical Research Institute at Virginia Tech, Roanoke, VA, United States, ²School of Neuroscience, Virgi, Blacksburg, VA, United States, ³University of Kentucky Medical Center, Kansas City, KS, United States, ⁴Department of Neurosurgery, Banner University Medical Center , Phoenix, AZ, United States, ⁵Department of Neurosurgery, Virginia Tech Carillion School of Medicine, Roanoke, VA, United States, ⁶Department of Physics, Virginia Tech, Blacksburg, VA, United States, ⁷Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA, United States

The decision-making process that drives food choice can potently modify overall health and disease risk. Studies, largely conducted in rodents, have underscored the importance of reward-related signals in the brain for guiding food choice. These signals can override homeostatic ones, and likely contribute to the ability of energy dense, highly palatable foods to drive poor health outcomes in humans. While many brain circuits have been implicated in the control of such reward-based eating, there is a growing consensus that it is steered by monoamine (dopamine, serotonin, and norepinephrine) release in brain areas like the amygdala. However, many of the key findings that support these ideas have yet to be translated to humans, due in large part to the lack of technologies that enable insights into the temporal dynamics of monoamine release in the human brain that are comparable to those provided by tools optimized for rodents. Recently, our group has been engaged in an effort to bridge this translational gap through the development of an approach that affords sub-second, concurrent detection of all monoamines in the brain of conscious humans. Here, we present results from on-going studies using this approach to study how monoamine neurotransmitter release in the human amygdala is modulated by food-predictive cues (n=10), as well as the valence of primary food rewards (n=8). Our data support a model whereby dopamine and serotonin signal food valence and cue-reward associations through unique patterns of opponent release. Collectively, these findings represent a first-of their kind test of the translatability of key findings from animal models and identify signatures of neurotransmitter release that may ultimately underwrite both adaptive and maladaptive food choices.

10:30

Control Of Ingestion By The Caudal Brainstem
Zachary Knight
University of California, San Francisco, San Francisco, CA, United States

The passage of food through the alimentary canal generates a series of feedback signals that are sensed by the brain and used to control feeding behavior. Many of these signals converge on the caudal brainstem, which contains the key neural circuits that drive meal termination. I will describe our work investigating the dynamics and function of these circuits during ingestion. A central theme is that these circuits control behavior by integrating layers of feedback signals from the mouth and gut. These feedback signals influence behavior both in real-time during ingestion and over longer timescales through learning.

11:00

To Be Determined
Read Montague

10:00

Genetic Architecture Of Ultra-Processed Food Consumption Links Neurodevelopmental And Metabolic Pathways To Habitual Diet
Filip Morys^1,2, Daiva E. Nielsen³, Lang Liu^1,4, Arsene Kanyamibwa⁵, Atheer Attar³, Tongzhu Meng³, Mari Shishikura¹, Annette Horstmann⁵, Alain Dagher¹
¹Montreal Neurological Institute, McGill University, Montreal, QC, Canada, ²Modern Diet and Physiology Research Center, Montreal, QC, Canada, ³School of Human Nutrition, McGill University, Montreal, QC, Canada, ⁴Department of Human Genetics, McGill University, Montreal, QC, Canada, ⁵Department of Psychology, Faculty of Medicine, University of Helsinki, Helsinki, Finland

Ultra-processed food (UPF) consumption is rising globally and is implicated in non-communicable diseases including cancer, metabolic disorders, and dementia. Engineered to optimize palatability, UPFs introduce sensory and metabolic properties that may drive consumption beyond that of traditional foods. Given that food preferences are heritable, UPF consumption may similarly reflect an underlying genetic architecture - yet this remains unexplored. Here, we present a genome-wide association study of UPF consumption in over 142,000 UK Biobank human participants with a polygenic score validation in an independent cohort. SNP-based heritability analysis revealed that UPF consumption is heritable (h² = 6.06%). We identified 15 genome-wide significant loci (p <5×10-⁸) mapping to 23 genes, most of which cluster within two major chromosomal inversions - 17q21.31 and 8p23.1 - linked to brain development and morphology, as well as FGF21, a gene associated with sugar and alcohol preference. A polygenic score derived from these associations significantly predicted UPF consumption in an independent validation cohort (n = 7,149, β = 0.59, p = 0.0002). Downstream analyses using Functional Mapping and Annotation of Genome-Wide Association Studies showed that UPF-associated genes are preferentially expressed in neurons and oligodendrocyte precursor cells of subcortical brain regions previously implicated in UPF intake. Significant genetic correlations with metabolic traits (fasting insulin, insulin resistance, blood lipid levels), anthropometrics, macronutrient intake, educational attainment, and self-control further highlight the broad physiological and behavioral mechanisms of UPF consumption. These findings reveal a neurobiological architecture underlying UPF intake with implications for diet-related disease prevention.

10:15

High-Fat Diet Remodels Vagal Sensory Pathways Through Inflammation To Promote Hyperphagia
Isadora Braga^1,2, Laryssa Oliveira Coutinho¹, Alan de Araujo^1,2, Rebeca Mendez^1,2, Claire de La Serre³, Dan Brierley⁴, Guillaume de Lartigue^1,2
¹Monell Chemical Senses Center, Philadelphia, PA, United States, ²University of Pennsylvania , Philadelphia, PA, United States, ³Colorado State University , Fort Collins, CO, United States, ⁴University College London, London, United Kingdom

Vagal sensory neurons sends meal-related signals from the gut to the brain to limit food intake. We previously found that short-term high-fat diet (HFD) rapidly causes vagal fiber withdrawal and impaired satiety, suggesting that peripheral sensory remodeling may drive overeating. We hypothesized that HFD induces inflammation-dependent vagal remodeling that disrupts gut-brain signaling. Methods: Vagal structure and nutrient-evoked NTS cFos were assessed in HFD-fed mice. Results: To test whether vagal remodeling is secondary to hyperphagia or triggered by diet itself, we pair-fed mice HFD to match chow-fed caloric intake. Despite matched intake, HFD reduced vagal fiber density and nutrient-induced NTS cFos, indicating that diet composition drives vagal remodeling and impaired gut-brain signaling (n=5/group, p=*). Because HFD causes low-grade inflammation, we gave the NSAID flurbiprofen twice daily during the first 3 weeks of HFD feeding. Flurbiprofen prevented vagal remodeling, preserved nutrient-induced NTS cFos (n=5/group, p=*), and blocked hyperphagia and excess weight gain (n=12/group, p=***), identifying inflammation as a key driver. Caloric restriction, diet reversal, and semaglutide failed to restore vagal structure or function, but VSG rescued both (n=6/group, p=*). Chemogenetic activation of NTS neurons suppressed food intake in HFD-fed mice (n=8/group, p=***), indicating that downstream circuits remain functional despite impaired vagal input. Conclusion: HFD induces inflammation-dependent remodeling of vagal sensory pathways independent of excess caloric intake, disrupting gut-brain satiety signaling and promoting hyperphagia. This defect originates in peripheral sensory pathways and is reversed by interventions that more broadly normalize the gut environment.

10:30

Methods Of Coding Food Into Nova Food Classes: Interrater Reliability Between A Reproduced Machine Learning Algorithm With Manual Coding
Laura Claire Walker^1,2, Amelia Blumberg^1,3, Eunice Chen¹
¹Psychology and Neuroscience, Temple University, Philadelphia, PA, United States, ²Winston Center on Technology and Brain Development, University of North Carolina at Chapel Hill Department of Psychology and Neuroscience, Chapel Hill, NC, United States, ³Ferkauf Graduate School of Psychology, Yeshiva University, New York, NY, United States

Rationale: Categorizing the degree to which food is processed is challenging. The NOVA food system groups food into 4 classes: (1) unprocessed/minimally processed foods, (2) processed culinary ingredients, (3) processed foods, and (4) ultraprocessed foods. Menichetti et al., (2023) developed a machine learning algorithm (MLA) to categorize foods into NOVA classes given their nutrient content. Researchers have also categorized food into NOVA classes using manual coding of nutrition food codes. Hypothesis: We hypothesized that there would be agreement between a reproduction of the MLA with and manual coding of NOVA classes. Methods: 24-hour food intake data was collected in-person in person for 105 healthy college students using the ASA24 Dietary Assessment Tool, 2024 (NCI, 2024) resulting in 2078 food items. The MLA (Menichetti et al., 2023) to categorize food into NOVA classes was reproduced (LCW); and items were manually categorized into NOVA classes (AB). Cohen’s κ was used to assess interrater reliability between the MLA coding and manual coding for each of the foods and drinks consumed, and for the average %s of total energy intake of each NOVA class for each participant. Results: Interrater reliability between the 2 methods for classifying NOVA classes for each food and drink item was κ=.63; for NOVA class 1, κ=.39; for NOVA class 2, κ=.56; for NOVA classes 3 and 4, respectively κ=.13 and .12. All findings were significant (p <.0001), with bootstrapping (1000 resamples) indicating stability. Conclusions: Interrater reliability for each food and drink item coded was substantial; moderate for NOVA class 2, fair for NOVA class 1, but slight for NOVA classes 3 and 4. These differences may be reflective of the distinct data types used by each method for classification.

10:45

Effects Of Controlled Diets High In And Free Of ULtraprocessed Food On The Brain Of Emerging Adults
Emma Leslie¹, Maria Rego², Monica Ahrens³, Wenjing Yu², Mary Elizabth Baugh¹, Anastasia Groccia⁴, Rhianna Sullivan¹, Han Lee¹, Ryann Kolb¹, Delbert Herald¹, Valisa Hedrick², Kevin Davy², Benjamin Katz⁵, Brenda Davy², Alexandra DiFeliceantonio¹
¹Fralin Biomedical Research Institute at Virginia Tech, Roanoke, VA, United States, ²Department of Human Nutrition, Foods, and Exercise at Virginia Tech, Blacksburg, VA, United States, ³Department of Internal Medicine, Division of Medical Informatics, Kansas City, KS, United States, ⁴School of Neuroscience at Virginia Tech, Blacksburg, VA, United States, ⁵Department of Human Development and Family Science at Virginia Tech, Blacksburg, VA, United States

The average American consumes 55% of their daily energy from ultraprocessed foods (UPF), which are created through industrial processes and contain additives not used in home kitchens. Emerging evidence links UPF consumption with adverse health outcomes including overweight and obesity, metabolic disease, and cancer. Adolescents are in a critical period for brain maturation and consume more UPFs than other age groups. Here, we aim to investigate if a diet high-in UPF alters brain response to a milkshake compared with a diet free-from UPF. In a crossover, randomized controlled trial participants (n=22) aged 18-25 completed two, 2-week controlled feeding periods including a UPF (81% UPF) diet and a NonUPF (0% UPF) diet. Before and after each diet intervention participants consumed a milkshake concomitant with functional magnetic resonance imaging (fMRI). Orbitofrontal cortex (OFC; [16, 28, -28], T=4.74, SVC pFWE = 0.033) response to milkshake receipt decreased after the UPF diet and increased following the NonUPF diet in adolescents (aged 18-21 years) but not young adults (aged 22-25 years). We next examined if change in brain response predicted intake and observed that entorhinal cortex ([-20 –8 –38], T=6.01, pFWE = 0.002 and [20 –6 –36], T=5.24, pFWE = 0.002) activity in response to milkshake consumption predicts intake at a subsequent ad libitum buffet regardless of the diet intervention or age. Entorhinal cortex receives projections from many areas previously demonstrated to predict intake. This work demonstrates UPF consumption may preferentially alter brain response to palatable foods in younger people.

11:00

A Western Diet Alters The Mitochondrial-Associated Transcriptome And Impairs Mitochondrial Bioenergetics In The Hippocampus Of Cognitively Impaired Mice (New Investigator Travel Awardee)
Ana L Loera-Lopez^1,2, Junwon Heo³, Magen N Lord², David L Miller^3,4, Jessica R Hoffman², Anson D Sing⁵, Tianyi Zhang⁶, Alexia King⁵, Eugene F Douglass⁷, Luke J Mortensen^4,6, Steven A Sloan⁵, Jarrod A Call^1,3,4, Emily E Noble^1,2
¹Neuroscience Graduate Program, Athens, GA, United States, ²Department of Nutritional Sciences, Athens, GA, United States, ³Department of Physiology and Pharmacology, Athens, GA, United States, ⁴Regenerative Bioscience Center, Athens, GA, United States, ⁵Department of Human Genetics, Emory, GA, United States, ⁶School of Chemical, Materials, and Biomedical Engineering, Athens, GA, United States, ⁷Pharmaceutical and Biomedical Sciences, Athens, GA, United States

Consuming diets high in saturated fats and added sugars, termed a Western diet (WD), is associated with cognitive impairment and neurodegenerative disease. Hippocampal-dependent cognitive functions are susceptible to both a WD and mitochondrial dysfunction. We hypothesized that a WD would alter mitochondrial bioenergetics in the hippocampus. C57BL/6J mice (total n=84) fed a WD, but not their chow-fed counterparts, displayed impaired hippocampal-dependent spatial memory in the Novel Location Recognition task (one sample t-test against chance levels). We conducted RNA sequencing of hippocampal neurons to elucidate transcriptomic changes related to mitochondrial functions followed by Virtual Inference of Protein-activity by Enriched Regulon (VIPER) analysis to predict changes to transcription factor (TF) activities. Finally, we measured mitochondrial function (i.e. respiratory conductance, enzyme activity, and antioxidant buffering capacity [AOxBC] of reactive oxygen species [ROS]). Statistical significance for gene expression data was defined as |log2FoldChange|>1 and p(adj)<0.05 and by Welch’s t-test p<0.05 for all other comparisons. Our results revealed a downregulation of all protein-encoding genes on mitochondrial DNA and of pathways related to mitochondrial complex I (MCI) in WD-fed mice. A WD also impaired MCI-based respiratory conductance and enzyme activity in hippocampal tissues. These findings were associated with a fragmented mitochondrial network, elevated ROS, and reduced AOxBC. Our VIPER analysis predicted decreased activity of TFs governing neural excitability. We conclude that WD consumption interferes with processes underlying mitochondrial bioenergetics in the hippocampus and provides insight into how a WD may contribute to cognitive dysfunction.

11:15

Prebiotic Supplementation Mitigates High-Fat Diet-Induced Disruption Of Estrous Cyclicity And Alters The Vaginal Microbiome.
Julia Cook¹, Jennifer Houston¹, Zowi Pogonat-Walters¹, Maja Legatt¹, Kellie Tamashiro², Claire de La Serre¹
¹Colorado State University, Fort Collins, CO, United States, ²Johns Hopkins University, Baltimore, MD, United States

Consumption of a high-fat (HF) diet has profound effects on female fertility, although the mechanisms underlying these effects remain poorly understood. There is evidence that diet can modulate the vaginal microbiome and disruption of the vaginal microbiome has been linked to increased susceptibility to infection and other adverse reproductive outcomes. In this study, we assessed the impact of HF feeding on reproductive health, using female Wistar rats (n = 6) fed either chow, HF (45% kcal from fat) or HF supplemented with prebiotic (resistant starch, RS) diets. HF diet consumption altered vaginal microbiome composition, including depletion of S.Marmotae compared to chow fed animals. HF-fed females also showed greater susceptibility to vaginal infection compared to chow fed females (p <0.05), measured by the number of days exhibiting infection patterns on estrous cytology slides and exhibited significantly increased estrous cycle length, indicating disrupted cyclicity. Prebiotic supplementation in HF fed females mitigated these effects, restored normal cycling patterns and reduced infection duration. Importantly, these changes occurred in the absence of detectable differences in body weight or alterations in gut to brain signaling, suggesting that female reproductive outcomes may be particularly sensitive to HF diet exposure even in the absence of typical metabolic or neural changes. Together, these findings support a model in which HF diet disrupts estrous cyclicity in association with vaginal microbiome remodeling, while prebiotic supplementation may provide protection against these effects.

1:00

To Be Gip Or Not To Be Gip, That Is The Question
Randy Seeley
University of Michigan

The advent of polyagonists has opened up tremendous new avenues for the pharmacological treatment of obesity. Numerous different combinations are being actively investigated. The gut hormone GIP and its associated receptor are active targets for polyagonists such as tirzepatide and retatrutide that demonstrate superior weight loss to GLP-1R agonists alone. These clear successes belie a dilemma. Reduced GIP receptor activity is associated with resistance to weight gain in mice and relative leanness in humans. Such genetic analyses support the notion that antagonizing the GIP receptor might be an appropriate strategy for weight loss medications. Maritide is a polyclonal antibody that serves as a GIP antagonist conjugated with two GLP-1 agonist peptides. In both pre-clinical and clinical data, maritide also leads to significant weight loss. How can we understand drugs that have the opposite effect on the GIP receptor, both being effective therapeutic strategies? This presentation will review a wide range of preclinical data to explore the underlying neural circuits for the actions of these drugs and explore the potential hypotheses that might resolve the dilemma presented by GIP.

2:00

Experimental Induction Of Uncertainty About Food Availability Over Two Weeks Impacts Brain, Behaviour, And Cognition In Humans. (Elsevier Physiology & Behavior New Investigator Travel Awardee)
Justin J Sung¹, Natasha Mattar¹, Noemie Saulnier¹, Laure Chaboussant¹, Filip Morys², Dana M Small^{1, 2, 3}
¹McGill University, Montreal, QC, Canada, ²The Neuro, Montreal, QC, Canada, ³Northwestern University, Evanston, IL, United States

Food insecurity (FI) affects around 700 million people world-wide and is linked to obesity, cardiovascular disease, and all-cause mortality. Animal models show that FI increases food intake, alters dopamine signaling, cognition and metabolism. Whether this translates to humans is unknown; however, epidemiological studies support this possibility and show that even “mild” FI – characterized as the experience of uncertainty in accessing sufficient food – leads to considerable negative health outcomes. Here we develop a novel paradigm to manipulate food uncertainty in healthy adults by varying food provision between 10% and 40% of estimated daily total energy expenditure over a 15-day experiment claiming to study the effects of food intake on cognition (n=15, 8 female and ongoing). Brain response to milkshake, impulsivity, risk tolerance, and ad libitum buffet meal intake was measured pre and post 6 lab days wherein participants underwent cognitive testing before and after a variable sized meal. Following the manipulation participants reported feeling uncertain whether the amount of food provided would be enough (μ=31.5, anchored 0= “not certain at all”, 100=”more certain than anything”). As predicted, the intervention increased ad libitum intake (p<0.001), produced a trending increased risk tolerance (p=0.06) and trending decrease in ventral striatal response to milkshake (pSVC=0.09). In addition, response in dorsolateral prefrontal cortex correlated positively with rated induced uncertainty (pFWE=0.03). This work provides preliminary support that food uncertainty can be experimentally manipulated in humans and that the experience may produce similar effects as observed in animal models. Data collection, including a control group with non-variable meals, is ongoing.

2:15

Early-Phase Ingestive Microstructure As A Behavioural Marker Of Semaglutide Response In Obesity: An Interim Analysis Of The Digrat Study (New Investigator Travel Awardee)
Michele Serra^1,3, Ahmed Al-Humadi², Werd Al-Najim², Daniela Alceste³, Nicole Jucker^1,3, Marco Bueter³, Carel le Roux²
¹Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich, Zurich, Switzerland, ²Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland, ³Department of Visceral Surgery, Hospital Maennedorf, Maennedorf, Switzerland

Current monitoring of GLP-1 receptor agonist therapy in obesity relies largely on body weight and may miss early treatment-related adaptation. We hypothesised that semaglutide induces early measurable changes in ingestive behaviour before longer-term clinical outcomes fully emerge, and that direct assessment of these adaptations may have future value for treatment monitoring in clinical practice. Adult females with obesity (BMI>30) initiating semaglutide (n=43) were studied alongside controls with untreated obesity (n=25) and controls with normal-weight (n=35). After an overnight fast, ingestive behaviour during consumption of a standardized liquid test meal was recorded under standardised conditions using a drinkometer and complemented by clinical assessments and visual analogue scales. Measurements were obtained at baseline and repeated follow-up visits after dose escalation. Interim analyses used non-parametric between-group comparisons and exploratory longitudinal models adjusted for baseline values and weight loss. Baseline macrostructural and microstructural ingestive parameters were largely comparable across cohorts with obesity. Semaglutide treatment was associated with improvements in body weight and adiposity. Behavioural changes were detectable early after treatment initiation and were most evident in burst-dependent ingestive measures, particularly during the first burst and early phase of the meal, whereas later intake phases and higher-order burst organisation showed alterations related to satiation. These interim findings support the feasibility of measuring ingestive behaviour to detect early treatment-related adaptation during semaglutide therapy and suggest potential value for mechanistic phenotyping and future clinical monitoring in obesity care.

2:30

Integrating Internal And External Signals To Optimize Food Decision Making (New Investigator Travel Awardee)
Yige Sun, Ahmed Bouteldja, Justin Sung, Zheyi Li, Filip Morys, Dana Small
Mcgill University, Montreal, QC, Canada

It is now well recognized that post-oral signals drive food reinforcement with distinct pathways associated with post-oral reinforcement for fat and carbohydrate. In the current study, we asked whether the type of fuel being used (i.e., nutrient partitioning) influences the reinforcement value of that fuel. In other words, when your body uses carbohydrates as a fuel, does this change how you value fatty or sugary foods? 28 participants with a healthy weight underwent fMRI-compatible indirect calorimetry (IC-fMRI) to estimate fuel use and performed an auction task to assess food reinforcement in the fMRI scanner. The type of fuel being used was determined by calculating the respiratory quotient (RQ) with a value of .7 reflecting fatty acid oxidation and a value of 1 reflecting glucose oxidation. In the food auction task, participants bid against a computer for the opportunity to eat foods comprised primarily of fat, carbohydrate, or their combination. Bid amount provided our measure of reinforcement value. A linear mixed-effects model including RQ, macronutrient category, their interaction, BMI, sex, age, and liking, with random intercepts for subject and food item, was performed to determine if fuel use was associated with food value. A significant RQ × macronutrient interaction emerged (β = 1297.79, p = .009), indicating that the relationship between fuel use and fuel value differed as a function of macronutrient content. Specifically, higher RQ was associated with lower bids for carbohydrate, but not fatty or combo foods. These findings demonstrate that fuel use influences the value of carbohydrates, revealing a novel association between nutrient partitioning and food reinforcement. Analyses are ongoing to investigate the neural correlates of this effect with fMRI.

2:45

Caloric Value Is Transferred To Anticipatory Cues As Interoceptive Predictions In Humans (George H.Collier New Investigator Travel Awardee)
Elayna Seago¹, Afroditi Papantoni¹, Jessica Liu^1,2, Kyle Burger¹
¹Monell Chemical Senses Center, Philadelphia, PA, United States, ²University of North Carolina, Chapel Hill, NC, United States

Cues in our environment that signal the presence of reinforcing foods become salient through conditioning, i.e., incentive sensitization. Little is known about the role of sugar and flavor and impact of weight status (BMI) on this process. We hypothesized that regions that encode reinforcement, salience, and gustatory interoception would show sensitization to cues over time and that this would be stronger in participants with higher BMI.Healthy adults (n=111; F=67; BMI=23.4±3) were exposed to cues and tastes of flavor-matched sugar-sweetened (SSB) and unsweetened beverages (USB) during an associative learning fMRI paradigm. Main effects of SSB taste > USB taste were performed across the whole brain. To assess conditioning, parameter estimates (SSB cue > USB cue) were extracted from 4 regions of interest (ROI), the midinsula (MI), dorsal striatum, ventral striatum and ventral pallidum, and the precuneus, at 4 time points (4 events per time point). Percent signal change was used in longitudinal multilevel models with tests for BMI moderation. In response to SSB taste (>USB taste), we observed bilateral amygdala activity extending into the ventral striatum (pFDR’s<0.005; Z’s > 4.3). We also observed an interaction between BMI and time (b=0.02; p=.012) where participants with a higher BMI showed greater cue sensitization in the MI. No significant effects were observed in the other ROIs. Greater change in MI response reflects amplified encoding of anticipated interoceptive signals of calories, particularly in individuals with elevated BMI. Alongside amygdala/ventral striatal response to SSB taste, this suggests that caloric value is encoded as an outcome and transferred to cues as interoceptive predictions, consistent with incentive sensitization beyond sensory features.

3:00

Translating The Gliotransmitter Octadecaneuropeptide Into A Once-Weekly Injectable Therapeutic, Dg-260, For The Treatment Of Obesity And T2Dm Without Adverse Events (Randall R. Sakai New Investigator Travel Awardee)
Keshav/S Subramanian¹, Oleksandra Orativskyi², Haley Maury², Drew Belser¹, Brandon Alonso¹, Ashley Lee¹, Chloe Do¹, Quindy Pan¹, Bart/C De Jonghe¹, Caroline/E Geisler³, Robert/P Doyle^2,4, Matthew/R Hayes¹
¹University of Pennsylvania, Philadelphia, PA, United States, ²Syracuse University, Syracuse, NY, United States, ³University of Kentucky, Lexington, KY, United States, ⁴Updstate Medical University, Syracuse, NY, United States

Obesity and type 2 diabetes mellitus (T2DM) are among the most common diseases but still lack effective long-term curative treatments.Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown astonishing effects in treating obesity and T2DM; however, they are associated with gastrointestinal adverse events, leading 2/3 of patients to discontinue their treatment within the first year and regain their lost body weight. Recent work from our lab showcased an octadecaneuropeptide (ODN) analog, tridecaneuropeptide (TDN), which acutely and chronically reduces bodyweight and improves glycemic control without nausea/emesis in rodents. Here, we present work on the development of a long-acting lipidated-TDN analog, DG-260, which potently reduces food intake and bodyweight in lean and diet-induced obese (DIO) mice upon acute systemic injection. In addition, using euglycemic clamps, DG-260 dramatically improves systemic insulin resistance in DIO mice through increased peripheral glucose clearance rates and insulin secretion. To evaluate the longitudinal impact of repeated DG-260 delivery, we measured daily high-fat diet (HFD) intake and bodyweight in DIO mice for 30 days receiving DG-260 injections every 48h in comparison to the GLP-1RA, semaglutide. DG-260 dose-dependently suppressed HFD intake and reduced bodyweight, culminating in reduced cumulative HFD intake and daily bodyweight loss comparable to the ~20% weight reduction of semaglutide. Furthermore, semaglutide-treated animals switched to DG-260 showed sustained bodyweight loss and HFD suppression. Lastly, dose escalation of DG-260 significantly increased the HFD intake and bodyweight reducing effects. Overall, these data show the enormous potential of DG-260 as an alternative, long-acting non-GLP-1 based therapeutic.

3:15

Stress Engages The Noradrenergic Brainstem-Hypothalamus Loop That Suppresses Appetite Persistently (New Investigator Travel Awardee)
Myungmo An, Junkoo Park, Sumin Lee, Se-Young Choi, Sung-Yon Kim
Seoul National University, 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. Inhibition of LC^NA neurons or their projections to the paraventricular hypothalamus (PVH) prevents stress-induced appetite suppression, whereas optogenetic activation of LC^NA neurons mimics stress effects that suppress feeding. Real-time norepinephrine recordings in the PVH show sustained elevation after restraint stress, correlating with the duration of feeding suppression. Pharmacological blockade of α1-adrenergic receptors abolishes stress-induced appetite suppression. Notably, this circuit is also required for feeding suppression after chronic stress. Our findings pinpoint the LC^NA-PVH^α1 noradrenergic circuit as a key driver of sustained appetite suppression following stress, uncovering a direct link between the brainstem arousal center and hypothalamic feeding circuits.

3:30

Single Nutrient Overconsumption Induces Nausea And Increases Gdf15 Levels In Rats, Effects Attenuated By Chronic Exposure To A Western Diet (New Investigator Travel Awardee)
Allison M. Pataro^1,2, Sophia L. Fischer^1,2, Serena X. Gao^1,3, Ann Law¹, Fatma Cicek¹, Madeline Medina^1,4, Tito Borner¹
¹Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, United States, ² Integrative and Evolutionary Biology Graduate Program, University of Southern California, Los Angeles, CA, United States, ³Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, United States, ⁴Bridging the Gaps Summer Research Program, Keck School of Medicine of USC, Los Angeles, CA, United States

Overconsumption of energy-dense foods plays a critical role in the development of obesity. Because of their high palatability, people may exceed the satiation threshold and overeat to the point of feeling nauseous, yet the relative contributions of volume versus nutrient composition to this response remain unclear. To begin disentangling these factors, we investigated how the overconsumption of a whole liquid meal or single macronutrient solutions affects satiation and malaise. Rats received gastric isocaloric and isovolumetric infusions of either a mixed-nutrient meal (Ensure), fat, sugar, or water. Subsequently, kaolin consumption (a proxy for nausea in non-vomiting rats), food intake, and plasma concentrations of GDF15, a cytokine known to promote nausea, vomiting, and anorexia, were measured. All gastric caloric infusions significantly reduced food intake, while water had no effect. Notably, isolated nutrient solutions induced kaolin intake and significantly elevated plasma GDF15 levels, whereas Ensure did not, indicating that nutrient composition rather than caloric load or volume drives nausea. Pharmacological blockade of serotonin receptors with ondansetron failed to attenuate nausea, suggesting a mechanism independent of serotonergic signaling. Importantly, in rats maintained on a high-fat/high-sugar diet, nutrient-induced kaolin consumption and elevated GDF15 levels following caloric load are significantly blunted. This suggests that exposure to a Western diet reduces overconsumption-induced malaise through blunted GDF15 signaling. Together, these findings identify GDF15 as a candidate mediator of nutrient-specific malaise and reveal that chronic exposure to energy-dense diets dampens this signaling system, potentially facilitating continued overconsumption.

3:45

In A World Of Protein Shakes And Glp-1S: Sex Divergent Effects Of Semaglutide On Muscle Composition And Protein Intake In Rats (Dorothy W. Gietzen New Investigator Awardee)
Mya A. Knappenberger¹, Madison T. Bento ², Morgan R. Sotzen², Suyeun Byun ¹, Annalise M. Kuhns ¹, Doris Olekanma¹, Karolina P. Skibicka²
¹The Pennsylvania State University, University Park, PA, United States, ² The University of Calgary, Calgary , AB, Canada

GLP-1-based anti-obesity therapies like semaglutide (SEMA) are widely used for weight loss, but their potential to reduce lean mass is intensely debated. How these treatments affect muscle function, composition and protein appetite and preference, and whether these effects differ by metabolic state or sex, remains unclear. We treated lean and diet-induced obese (DIO) rats with SEMA for 4 weeks and compared their muscle mass with ad libitum control and pair-fed (PF) rats (n=12/group). SEMA reduced gastrocnemius mass in lean and DIO males (-11%, -8% vs. controls, p<0.05), but not females, indicating an obesity-independent sex difference. In DIO rats, control males improved wire hanging over time, whereas SEMA-treated males did not, suggesting impaired muscle function. In contrast, SEMA-treated females improved muscle function, which correlated with lower body weight, suggesting that reduced body mass may partly underlie this effect. Given the relationship between protein intake and muscle function, we determined whether SEMA affects protein preference. Lean, but not DIO, SEMA-treated rats increased their protein preference in a sex-independent manner. Motivated behavior for protein consumption, assessed by PR operant test for high vs low protein, was not altered across groups. SEMA-treated DIO males also showed reduced protein preference in a macronutrient preference test (7.36 vs. 12.45 kcal, ~40% decrease, p<0.05), an effect not observed in females. These findings suggest that protein preference is differentially regulated by biological sex and metabolic state and suggest impaired protein prioritization in males, when competing nutrients are available. These findings reveal sex-specific and largely obesity independent effects of SEMA on muscle and protein appetite.

10:00

Lateralized Vagal Circuits Control Feeding
Alan de Araujo¹, Isadora Braga^1,2, Gabriel Tofani^1,2, Laryssa Coutinho¹, Mingxin Yang^1,2, Guillaume de Lartigue^1,2
¹Monell Chemical Senses Center, Philadelphia, PA, United States, ²University of Pennsylvania, Philadelphia, PA, United States

Vagal sensory neurons in the nodose ganglia (NG) convey gut-derived signals to the brain to control eating. Despite this central role, vagal circuits have historically been considered bilaterally redundant. Emerging evidence that gut-vagal signaling can drive dopamine release through the right vagus nerve challenges this view and suggests functional lateralization. We hypothesized that left and right NG neurons (LNG and RNG) detect distinct meal-related signals and control complementary aspects of ingestive behavior. Methods: We combined single-nucleus RNA sequencing, behavioral assays, and brain-wide activity mapping in mice. Results: snRNA-seq of nodose neurons revealed widespread transcriptional asymmetry between LNG and RNG, with chemosensory-enriched cells biased toward the RNG and mechanosensory-enriched cells biased toward the LNG. Restricting analysis to gut-innervating neurons preserved this organization, indicating that laterality is embedded within intestinal vagal circuits. Chemogenetic stimulation and caspase-mediated ablation revealed that the RNG, but not LNG, was necessary and sufficient for fat-associated memory recall after memory decay. Conversely, the LNG, but not RNG, was necessary and sufficient to induce distension-induced satiety and suppress subsequent intake. Consistently, optogenetic stimulation of LNG and RNG neurons recruited distinct central circuits: RNG stimulation significantly increased hippocampal activity, whereas LNG stimulation activated hypothalamic nuclei involved in homeostatic feeding control. Conclusion: This work identifies functionally specialized, lateralized vagal NG populations that differentially encode meal-related signals and provides a mechanistic framework for how gut-derived signals guide ingestive behavior.

10:15

Molecular Mechanisms For Sensing Stomach Distension
Avnika Bali^1,2, Isadora Braga^1,2, Guillaume de Lartigue^1,2
¹Monell Chemical Senses Center, Philadelphia, PA, United States, ²University of Pennsylvania, Philadelphia, PA, United States

Gut distension signals give rise to feelings of fullness and meal termination as well as parasympathetic processes such as gastric emptying, gut motility, thermoregulation and glucose homeostasis. Vagal afferent neurons (VANs) are known to respond to diverse mechanical signals in the gut and suppress feeding. Mechanical forces including tension, relaxation, pressure and flow likely require specialized mechanoreceptors and may be conveyed through distinct neuronal pathways, but the molecular mechanisms that transduce these mechanical stimuli are poorly defined. We therefore hypothesized that a heterogenous class of mechano-transducers define separate mechanosensory populations that affect disparate behavioral and physiological processes. Results: Using in vivo Ca2+ imaging combined with multiplexed FISH in mice with intragastric balloons, we identified Piezo2 and TRPA1 as candidate mechanosensitive ion channels expressed in non-overlapping populations of stretch-responsive VANs. These populations are distributed across canonical receptor-defined vagal subtypes, including Glp1r- and Oxtr-expressing neurons. To directly test function, we selectively deleted Piezo2 or TRPA1 in stomach-innervating VANs. Loss of either channel contributes towards distension-induced reduction in food intake and locomotion. In contrast, only Piezo2 was required for distension-induced autonomic responses. All experiments were performed in mice (n= 5-8 per group). Conclusions: These findings identify Piezo2 and TRPA1 as key molecular transducers of gastric distension in distinct vagal mechanosensory populations, revealing parallel pathways that differentially regulate behavioral and autonomic components of eating and homeostasis.

10:30

Encoding Of Interoceptive State By Paraventricular Thalamic Ensembles
Jared Butts¹, Samuel Congdon^1,2, Vraj Patel¹, Qingyin Zheng², Patrick Sweeney^1,2
¹Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL, United States, ²Department of Molecular and Integrative Physiology, University of Illinois Urbana-Champaign, Urbana, IL, United States

Organisms must constantly assess internal state and external stimuli to identify need state and drive motivated behavior. The paraventricular nucleus of thalamus (PVT) is a midline thalamic structure known to integrate interoceptive and exteroceptive cues and promote ingestive behavior via its connectivity with canonical homeostatic centers. However, the population and single-neuron level encoding of homeostatic perturbations within the PVT have yet to be fully described. Here, we utilized a pan-neuronally expressed calcium indicator combined with in vivo microendoscopy in behaving animals (n=12 C57BL/6J mice, 6 male & 6 female) to longitudinally characterize PVT responses to diverse homeostatic challenges. In a multisession fast-refeeding paradigm, we identified three stable responses to chow: neurons that are 1) highly active in the fasted state and inhibited by food consumption, 2) transiently activated during consumption, and 3) activated following the bulk of consumption. Internal state and food palatability modulate PVT encoding of ingestion, as pretreatment with semaglutide attenuated chow responses while high fat diet increased their magnitude. These responses are stable across need states, as the consumption of a liquid diet in the fasted state and water following water deprivation induced similar responses at the individual cell level. Consistently, neurons that exhibited increased activity in the fasted and thirsty state were activated by acute cold exposure, while neurons that increase activity during a refeed and water access were inhibited by cold, indicating selective tuning to state and stimulus valence. Thus, we have identified a unique homeostatic nucleus that bidirectionally encodes valence across vastly different behaviors and states.

10:45

Urocortin-3 Suppresses Food Intake And Intestinal Inflammation Via An Enteroendocrine Gut-Brain Circuit
Giulia T. Uhr^1,2,3, Lavinia Boccia^2,3, Niklas Blank^4,5, Timothy O. Cox¹, Lenka DohnalovÃÂÃÂ¡¹, Haohan Karen Wei¹, Kaitlyn Mcelhern^2,3, Carol Rau^2,3, Stephen Wisser¹, Leonel Joannas^6,7, Jorge Henao-Mejia^6,7, Maayan Levy^4,5, J. Nicholas Betley^2,3, Christoph A. Thaiss^4,5
¹Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, ²Department of Biology, University of Pennsylvania, Philadelphia, PA, United States, ³Department of Neuroscience, Perelman School of Medicine, Philadelphia, PA, United States, ⁴Arc Institute, 3181 Porter Dr, Palo Alto, Palo Alto, CA, United States, ⁵Department of Pathology, Stanford University, Palo Alto, CA, United States, ⁶Department of Pathology and Laboratory Medicine,, Philadelphia, PA, United States, ⁷Institute for Immunology and Immune Health (I3H), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

Intestinal enteroendocrine cells (EECs) sense luminal signals and regulate whole-body physiology. Whether EECs also play a role in the regulation of intestinal inflammation and responses to infection remains unclear. We hypothesized that activation of irritant-sensing EECs engages a gut-brain pathway that suppresses food intake and protects against intestinal inflammation. Using mice, we combined chemogenetics, peptide administration, colitis models, organoid culture, and neural activity mapping to characterize this gut-brain circuit linking nutrient sensing to the regulation of feeding and intestinal immunity. Activation of the irritant receptor TRPA1 in EECs increased release of urocortin-3 (UCN3), a ligand for CRHR2-expressing vagal afferents. Activation of this pathway suppressed hypothalamic AgRP neuron activity and reduced food intake, thereby lowering inflammatory monocyte infiltration. In dextran sulfate sodium-induced colitis, UCN3 signaling decreased inflammatory monocyte infiltration and improved disease outcomes, whereas genetic or chemogenetic disruption of UCN3–CRHR2 signaling exacerbated inflammation. Importantly, UCN3 reduced feeding without inducing aversive malaise behaviors, in contrast to classical anorectic pathways. Mouse treatment groups ranged in size from n = 3 to 12. Statistical analyses included unpaired two-tailed t-tests or ANOVA with post hoc comparisons, with significance set at p <0.05. These findings identify a previously unrecognized EEC-mediated gut-brain circuit that links nutrient sensing to the coordinated regulation of feeding and intestinal immunity. This pathway may represent a new therapeutic target for obesity and inflammatory bowel disease with reduced adverse effects compared to existing treatments.

11:00

Associations Between Interoceptive Awareness And Appetitive Traits In Children With Overweight Or Obesity (New Investigator Travel Awardee)
Allison M. Boyar^1,2, David R. Strong³, Kyung E. Rhee⁴, Kerri N. Boutelle^2,3,4
¹San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, United States, ²Department of Psychiatry, University of California San Diego, San Diego, CA, United States, ³Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, San Diego, CA, United States, ⁴Department of Pediatrics, University of California San Diego, San Diego, CA, United States

Interoceptive awareness (IA), the ability to perceive bodily signals, regulates eating behavior. We hypothesized increased IA of internal cues would be associated with stronger satiety responsiveness (SR) and weaker reactivity to external food cues in children with overweight or obesity (OW/OB). 121 children (mean age = 10.65 ± 1.66 years; mean %BMIp95 = 112.11 ± 13.88; 68.6% female; 48.8% White, 25.6% Hispanic/Latino, 25.6% other) counted self-perceived heartbeats during 3 intervals compared to electrocardiogram recording. Concordance scores ranged from 0-1 (higher = better IA). Parents reported child eating behaviors via Eating in the Absence of Hunger and Child Eating Behavior questionnaires. Regression models adjusted for child and parent demographics, %BMIp95, and parent BMI when estimating associations of IA with reactivity to internal (SR; NAE: negative affect eating) and external cues (FR: food cue responsiveness; EE: external eating). In support of hypotheses among children with mid-range levels of IA, higher IA was associated with lower levels of FR (b = −3.40, p = .001) and EE (b = −2.42, p = .011). However, children with the highest levels of IA had lower levels of SR (b = −2.53, p = .035) and higher levels of FR (b = 3.54, p = .012) and EE (b = 2.75, p = .035). No associations were observed between IA and SR, NAE, FR or EE within the lowest range of IA (ps > .149). Moderate IA may represent an optimal regulatory range, buffering reactivity to external food cues. High IA may reflect true sensitivity, attentional bias, or misattribution of internal signals when assessing satiety and may heighten learning of salient food cues. IA may be a modifiable target when addressing overeating driven by appetitive traits in children with OW/OB.

11:15

Evaluation Of A Two-Stage Water Loading Test To Measure Gastric Interoception In Children
Emily Hohman, Orfeu Buxton, Kathleen Keller
Penn State University, University Park, PA, United States

Individual differences in interoception (internal state sensing) may contribute to obesity risk, but objective measures are limited. We evaluated the two-stage water loading test (WLT-II) as a measure of gastric interoception in children and related this measure to the Multidimensional Assessment of Interoceptive Awareness-Youth (MAIA-Y) and Interoception Sensory Questionnaire (ISQ) measures. In stage 1 (satiation), 7–10-year-olds (n=53) were instructed to drink water from an opaque bottle through a straw until they felt as if they had eaten ‘just enough’; in stage 2 (fullness), they drank additional water until completely full. The volume of water to reach satiation as a percentage of total volume consumed (%sat) is an index of gastrointestinal interoception that is independent of stomach volume; higher %sat reflects poorer interoception. Children drank 125 ± 88 ml (mean ± SD) in stage 1 and 136 ± 93 ml in stage 2; %sat was 48 ± 15% (range 17-82%). Mean %sat was higher in girls than boys (52 vs. 45%, p=0.06) and in younger (7-8) vs. older (9-10 years) children (54 vs. 45%, p=0.03). Greater interoceptive difficulty (ISQ) was associated with higher %sat in the full sample (r=0.26, p=0.06) and among older children (r=0.40, p=0.02). Among older children only, MAIA-Y Noticing Body Sensations was negatively associated with %sat (r=-0.39, p=0.03). MAIA-Y Body-Listening was associated with lower %sat (r=-0.37, p=0.06) in girls, but was unexpectedly associated with higher %sat (r=0.44, p=0.03) among boys. The WLT-II is feasible in children and correlates with self-report measures of interoception, though not all in expected directions. Future analyses will examine associations between %sat and cardiac interoception, eating behaviors, and adiposity.

10:00

Central Amygdala Glucagon-Like Peptide 1 Receptor Neurons Integrate Endogenous Glp-1 And Encode Consummatory Valence Through Diverse Outputs
Miguel Duran¹, Jennifer Willis¹, Sai Pochana¹, Nilay Dalvi¹, Anusha Polamarasetty¹, Melissa Rodriguez¹, Kirk Habegger², J. Andrew Hardaway¹
¹Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States, ²Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States

Pharmacotherapies targeting GLP-1 receptors (GLP-1Rs) are transforming diabetes treatment. Despite the rapid adoption of GLP-1 analogs in the clinic, our understanding of the endogenous GLP-1 and GLP-1R system, particularly in the limbic system, has not kept pace. We used Glp1r-Cre; Gcg-FlpO mice to label GLP-1R neurons in the central amygdala (CeA, Glp1r^CeA) and GLP-1-producing neurons in the nucleus of the solitary tract (Gcg^NTS) with eGFP and TdTomato respectively. We then used tissue clearing combined with light sheet microscopy to quantify proximity of Glp1r^CeA soma to Gcg^NTS axons and whole brain outputs of Glp1r^CeA and Gcg^NTS neurons. We identified Glp1r^CeA axons in thalamic, hypothalamic, midbrain, and brain stem nuclei. Using optogenetic-assisted mapping in ex vivo brain slices and electrophysiology, we detected functional inhibitory connections in a subset of these nuclei. Within the CeA, Glp1r^CeA neurons inhibit >50% of recorded medial CeA (CeM) cells and bath application of GLP-1 enhances this inhibition. We then used immunofluorescence to detect GLP-1R protein on CeM neurons. Consistent with the presence of GLP-1R protein in the CeA, bath application of GLP-1 resulted in persistent inward currents and significant depolarization. Using fiber photometry in Glp1r^CeA neurons, we observed the activation of these neurons in response to aversive stimuli, tastants, or ramping during appetitive behavior. Food consumption; however, was coupled with a significant decrease Glp1r^CeA neuron activity. Finally, we used chemogenetic inhibition and observed that activation or inhibition of Glp1r^CeA neurons reduced or increased high fat diet consumption respectively. We conclude that Glp1r^CeA neurons integrate endogenous GLP-1 inputs and serve as a brake on palatable food intake.

10:15

Top Down Regulation Of Feeding And Body Weight By Mc4R In The Mpfc
Michaela Cooke¹, Priyanka Das¹, Maddy Smith¹, Rachel Ross^1,2
¹Albert Einstein College of Medicine, Bronx, NY, United States, ²Montefiore Medical Center, Bronx, NY, United States

Body weight (BW) maintenance depends on coordinated regulation of feeding, locomotion, thermogenesis, and baseline energy use involved in autonomic regulation. Clinical studies implicate medial prefrontal cortex (mPFC) dysfunction in obesity and in eating disorders across the weight spectrum, but the functional roles of its subregions in feeding and energy balance remain poorly defined. The melanocortin-4 receptor (MC4R), a brain-expressed GPCR critical for energy homeostasis, has been studied primarily in hypothalamic circuits. Here, we hypothesize MC4R functions differently in dorsal and ventral mPFC subregions in response to metabolic state change, as we found that expression of the peptide varies with satiety. Using region-specific deletion in male MC4Rlox/lox mice, with data analyzed by ANOVA with multiple comparison tests, we find opposing effects on BW: loss of MC4R in ventral mPFC (vmPFC) increases BW (n=15), whereas deletion in dorsal mPFC (dmPFC) decreases BW (n=12) compared to controls. However, both manipulations reduce fasted-state locomotion with no change in fed state. Preliminary calorimetry suggests dmPFC MC4R signal promotes energy expenditure in male mice, while vmPFC MC4R signal favors energy conservation in both sexes. Consistent with this, dmPFC MC4R neurons preferentially project to locomotor and effort-related regions (medullary pyramids, periaqueductal gray), whereas vmPFC MC4R neurons target circuits regulating consummatory behavior (lateral septum, medial preoptic area, substantia innominata, nucleus accumbens shell). Together, these findings indicate that MC4R signaling in distinct mPFC subregions oppositely regulates energy balance through separable behavioral and circuit mechanisms which may play a role in disordered eating and body weight.

10:30

Glp-1R Agonism Modulates Lipid-Induced Neutrophilia Via An Area Postrema-Independent Mechanism
Anna Parolini¹, Sophia Fischer², Tito Borner², Giuseppe Danilo Norata¹, Andrea Baragetti¹
¹Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy, ²Department of Biological Sciences, University of Southern California, Los Angeles, CA, United States

High-fat diet (HFD) feeding induces metabolic dysfunction and systemic inflammation. Transitions between fasting and feeding, which engage GLP-1R signaling, trigger rapid metabolic shifts that subsequently activate inflammatory immune responses. However, whether GLP-1R signaling links nutrient ingestion to postprandial immune-inflammation, and through which mechanism, remains unknown. Here we tested whetherGLP-1R activation impacts innate immune-inflammation during acute and chronic HFD challenges and whether this effect is mediated by the area postrema (AP), a key hindbrain node for GLP-1 signaling. To assess GLP-1R signaling impact on lipid-induced postprandial immune-inflammation, Sprague-Dawley rats were fasted overnight and then subjected to intragastric fat gavage two hours after pretreatment with semaglutide (10nmol/kg). Blood immunophenotyping was performed in both chow- (n=8/group) and HFHS-fed (45% kcal from fat, 20% kcal from carbs; n=4/group) rats. To evaluate AP-mediated immunometabolic modulation, rats underwent AP lesion (APX ; n=8) or sham surgery (n=8), followed by acute HFD refeeding post-fasting. A single fat gavage in prominent increase in circulating neutrophils versus controls, while semaglutide pretreatment attenuated acute lipid-induced circulating neutrophilia in both chow- and chronic HFHS-fed rats. In APX rats undergoing acute HFD refeeding, neutrophilic responses matched those of sham-operated controls. GLP-1R activation modulates fat-induced neutrophilia independently of the area postrema. We propose GLP-1 as a novel potential regulator of immunity beyond its metabolic actions, highlighting immunometabolic crosstalk whereby GLP-1 could bridge systemic metabolism and postprandial innate immune responses.

10:45

Effects Of Gcg-Derived Peptide Signaling On Body Composition And Caloric Intake
Inge E Guerrero, Michelle B Bales, Eva H Rucinski, Mary A Raker, Linda Rinaman
Florida State University, Tallahassee, FL, United States

Western diets (WD) tend to be calorically dense, relatively high in fat and sugar, and relatively low in protein, all of which likely contribute to WD-induced increases in obesity and metabolic disease. The glucagon gene (Gcg) encodes preproglucagon, which is cleaved into glucagon-like peptide-1 (GLP-1) and related peptides that regulate appetite and energy balance. While synthetic GLP-1 receptor agonists suppress WD intake and BW, the role of endogenous GLP-1 and related peptides remains unclear. We used genetic knockdown (KD) of Gcg to disrupt preproglucagon-derived peptide signaling and assess effects on food choice, caloric intake, and body composition in rats. EchoMRI was conducted before and after 8 weeks of diet exposure. At 6wks of age, male and female KD and wild-type (WT) rats were group-housed and assigned to chow (C) alone (Lab Diet 5001) or to a choice of C and WD (Research Diets D12079B) for 8 wks. Average kcal intake per cage of group-housed rats was calculated weekly and compared between the two diet conditions, and separately within the C+WD choice groups. KD rats of both sexes consumed significantly more kcal and gained significantly more BW than WT rats, with an additional main effect of diet on BW gain and a trending effect of diet on kcal intake in females. WD-fed KD rats gained significantly more fat mass than WD-fed WT rats. For rats in the food choice group, male KD rats consumed more WD-derived kcals than WT males and showed a greater preference for WD vs. C; a similar trending effect of genotype was seen in females. These findings demonstrate that endogenous Gcg-encoded peptide signaling is linked to increased food intake and fat mass in rats, with some apparent sex differences.

11:00

Primary Cilia Adcy3 Is Necessary For Dmvmh Leptin Effects On Feeding
Christopher Petty¹, Austin Mills², Magen Lord², Ruth Harris³, Emily Noble^1,2
¹Neuroscience Graduate Program, University of Georgia, Athens, GA, United States, ²Department of Nutritional Sciences, University of Georgia, Athens, GA, United States, ³Department of Physiology, Augusta State University, Augusta, GA, United States

Leptin acts in the dorsomedial ventromedial hypothalamus (dmVMH) to reduce food intake, but this function of leptin is reduced in obesity. Neurons in the dmVMH contain primary cilia, which are organelles that contain concentrated G protein-coupled receptors whose signals are transduced via adenylyl cyclase type 3 (ADCY3). Leptin increases ADCY3 in the hypothalamus, and ADCY3 signaling necessary for anorexigenic responses of some hypothalamic neuropeptides. Whether leptin modulates ADCY3 in the dmVMH and/or requires ADCY3 to modulate food intake in this region is unknown. We hypothesize that leptin increases primary cilia ADCY3 in the dmVMH, and that ADCY3 is necessary for leptin mediated food intake reductions. Our results in male Sprague Dawley rats show that peripheral leptin administration at dose effective for reducing food intake elevates pSTAT3 in dmVMH primary cilia containing neurons and increases ADCY3 positive ciliary length and number (n=8/group; Student’s t-test; P<0.05). To determine whether ADCY3 is necessary for leptin mediated reductions in food intake, virogenetic knockdown of ADCY3 was used. ADCY3 knockdown in the dmVMH increased food intake and body weight (n=12/group; Two-way ANOVA, Fishers LSD; P<0.05), with no differences in energy expenditure in male SD rats. Leptin in the dmVMH reduced food intake in control animals, but not in animals with ADCY3 knockdown, suggesting that ADCY3 is necessary for leptin-mediated food intake reduction. Our findings provide mechanistic insight for how leptin signals to reduce food intake and may be important for understanding how the effectiveness of leptin is impacted by internal state.

11:15

Neuropeptide Y1 Receptor-Expressing Neurons In The Paraventricular Hypothalamus Link Hunger And Reward Circuits To Drive Feeding
Sam Z Bacharach¹, Katie A Zappetti^{1, 2}, Laryssa O Coutinho¹, Zhongwu Liu³, Marcelo O Dietrich³, Amber L Alhadefff^{1, 2}
¹Monell Chemical Senses Center, Philadelphia, PA, United States, ²University of Pennsylvania, Philadelphia, PA, United States, ³Yale School of Medicine, New Haven, CT, United States

Agouti-related protein (AgRP)-expressing neurons in the arcuate nucleus are tuned to hunger state and are critical for feeding behavior. Stimulation of AgRP neurons robustly drives food intake and increases nucleus accumbens (NAc) dopamine (DA) release to food. However, the circuit mechanisms linking AgRP neurons to mesolimbic DA remain poorly understood, limiting our ability to explain how hunger governs food-driven motivation. We first tested whether AgRP neuron activation alters synaptic input onto ventral tegmental area (VTA) DA neurons. Chemogenetic excitation of AgRP neurons in mice (n=12) decreased IPSC frequency in VTA DA neurons, suggesting a decreased inhibitory tone onto VTA DA neurons. This provides a synaptic mechanism by which hunger enhances DA responses to food. AgRP neurons do not project directly to the VTA, so to identify the circuit mechanisms connecting the two, we optogenetically stimulated seven major AgRP projection targets while recording DA release in the NAc (n=75). Stimulation of AgRP terminals in the paraventricular hypothalamus (PVH) phenocopied AgRP cell body activation, robustly increasing DA release to food and driving feeding. Because AgRP neurons co-release NPY, we hypothesized that AgRP neurons inhibit Y1 receptor-expressing (Y1R) neurons in the PVH to reduce inhibitory tone onto VTA DA neurons. We used RNAscope and in vivo calcium imaging to show that AgRP neuron activation suppressed PVH Y1R neuron activity (n=14). Moreover, DREADD-mediated inhibition of PVH Y1R neurons increased NAc DA release to food and promoted feeding (n=9). We used ANOVA with post hoc t-tests to analyze all data. Together, these findings identify PVH Y1R neurons as a critical intermediary connecting hunger signals to mesolimbic DA circuits to promote feeding.

1:00

Understanding Pomc Neurons Heterogeneity In Energy Balance And Beyond
Daniela Cota
INSERM, Neurocentre Magendie, U1215, University of Bordeaux, Bordeaux, France

Hypothalamic pro-opiomelanocortin (POMC) neurons are critical regulators of energy balance. By integrating adiposity and nutrient signals, they classically act to restrain food intake and promote energy expenditure via melanocortin signaling. Genetic disruption of POMC in mice and humans produces hyperphagia and severe, early-onset obesity, underscoring that intact POMC neuron function is indispensable for defending against positive energy balance and obesity pathogenesis. Nevertheless, recent evidence demonstrates that POMC neurons are molecularly and functionally heterogeneous, can stimulate feeding under specific conditions, and become active before food consumption, therefore challenging the traditional view of their satietogenic function. Here I will present published and unpublished data we have generated illustrating the complex roles of hypothalamic POMC neurons in energy balance and beyond.

3:00

Dietary Substitute Sugars&Rsquo; Osmotic Signaling Engages An Ileal Brake To Control Gut Motility And Feeding Via Glp-1�
Arthur Beyder
Enteric Neuroscience Program (ENSP), Division of Gastroenterology and Hepatology, Departments of Medicine and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States

Modern diets are replete with poorly absorbed sugar substitutes like sugar alcohols (e.g., xylitol) that impose unusually high luminal osmolar loads, yet how the gut senses these non-nutritive osmoles to regulate ingestion is unclear. Here, we show that luminal hyperosmolarity triggers an ileal brake–like response that slows proximal gut transit and suppresses feeding via gut hormone release. In mice, acute gavage of xylitol (vs. iso-osmotic control) caused luminal contents to accumulate in the small intestine while less reached the cecum within ~45 min, indicating region-specific slowing of ileal transit. This occurred alongside a local spike in ileal luminal osmolality (while stomach and colonic contents remained near isotonic), a ~2-fold surge in plasma GLP-1, increased gastric volume (gastric accommodation), and ~60% reduction in short-term food intake, which are all hallmarks of an ileal brake response. We focused on ileal sensing mechanisms and GLP-1–secreting enteroendocrine cells (EECs), which are known coordinators of the ileal brake, as candidate osmosensors. Mechanistic studies showed that hyperosmolar conditions directly excite EECs: patch-clamp recordings from a human L-cell model (QGP-1) revealed a dramatic ~40 mV depolarization and evoked action potentials under hyperosmotic (400 mOsm/kg) vs. iso-osmotic conditions. Similarly, ileal, but not colonic, primary EECs exhibited robust Ca�⁺ influx to hyperosmolar stimuli ex vivo, and hyperosmotic exposure of ileal organoids triggered a 2–3� increase in GLP-1 secretion. These findings identify an ileal epithelial osmosensory pathway that couples luminal hyperosmotic stimuli to L-cell hormone release and gut-brain-gut feedback. By engaging this pathway, non-nutritive osmoles can powerfully modulate GI motility and satiety signals, revealing a mechanistic link between acute exposure to dietary osmolarity and ingestive behavior. Together, these findings reveal dietary osmolarity as a powerful, previously underappreciated signal through which the gut translates modern food composition into hormonal control of motility, satiety, and ingestive behavior.�

3:30

The Role Of Gastrointestinal Mechanosensation In Regulating
Britya Ghosh¹, Catherine Calhoun², Kara Marshall^1,3,4
¹Department of Neuroscience, Baylor College of Medicine, Houston, TX, ²Rice University, Houston, TX, ³Department of Neuroscience, Howard Hughes Medical Institute, ⁴Jan and Duncan Neurological Research Institute at Texas Children�s Hospital, Houston, TX

The stomach distends to accommodate food, and the gastrointestinal (GI) tract is in constant motion as the ingested food is propelled forward. Mechanical cues from the gastrointestinal (GI) tract play an essential role in informing the brain of feeding states and regulating energy homeostasis, yet it is not well studied. While chemosensory signals, such as leptin and ghrelin, are well known, how mechanical signals induced by stomach distention contribute to energy homeostasis remains poorly defined. PIEZO1 and PIEZO2 are mechanosensory ion channels which are expressed in different organs throughout the body, including neurons that innervate the gastrointestinal tract. They open in response to mechanical force and relay mechanosensory signals via the peripheral nervous system, and are excellent candidates for the sensors that detect mechanical signals to control food intake. Previous work identified oxytocin-receptor�expressing (Oxtr+) sensory neurons as key mechanosensors that detect stretch and relay the sense of satiety to the brain. We are using Oxtr-Cre animals in combination with other genetic tools to delete PIEZO ion channels from subsets of sensory neurons and delineate how these ion channels function to modulate food intake. We found that loss of Piezo2 in Oxtr+ neurons, as well as more broadly in the sensory nervous system, altered feeding patterns despite normal body composition. We further examined hypothalamic neurons in the arcuate to determine how central feeding circuitry was engaged in the absence of mechanosensory signaling. By revealing a mechanosensory pathways parallel to established chemosensory systems, these findings open avenues for developing next-generation anti-obesity therapeutics that tap into mechanical signaling besides targeting the chemical pathways which, despite their efficacy, carry significant gastrointestinal and systemic side effects.

4:00

Pharyngeal Mechanosensation Drives Rapid Thirst Satiation
Sung-Yon Kim
Seoul National University, Seoul, South Korea

Drinking rapidly quenches thirst within seconds, a critical pre-systemic feedback that occurs well before absorbed water restores systemic balance. However, the sensory origin and neural mechanism underlying this rapid thirst satiation have remained elusive. Here, we dissociated tightly coupled processes of drinking to reveal that pharyngeal mechanosensation during the swallowing reflexes is the source of this rapid thirst satiation. This signal primarily depends on PIEZO2 in the nodose-jugular-petrosal ganglia and ascends through a pathway linking the nucleus of the solitary tract, parabrachial nucleus, and median preoptic area, ultimately inhibiting subfornical organ thirst neurons. Computational modeling and experiments reveal that this circuit operates as a high-pass filter, selectively transmitting swallowing-evoked signals only when they occur in rapid succession, a characteristic of drinking. Our findings pinpoint the long-sought sensory origin of rapid thirst satiation and delineate the pharynx-to-forebrain circuit that transforms swallowing signal into drinking-specific inhibition to quench thirst.

3:00

High-Fat Diet Exposure Alters Sucrose Consumption Behaviors And Dopamine Signaling In The Nucleus Accumbens
Claire M. Corbett¹, Leighelle Adrian¹, Brianna E. Linneman^1,2, Samantha L. Bozarth^1,2, Mark Niedringhaus^1,2, Elizabeth A. West^1,2
¹Rowan-Virtua University School of Osteopathic Medicine, Stratford, NJ, United States, ²Rowan-Virtua School of Translational Biomedical Engineering and Sciences, Stratford, NJ, United States

With increased consumption of diets high in fat in modern societies, it is critical to consider the effects of diet on behavior and brain function. Here, we examined how a history of a high-fat diet alters reward processing, associative learning, and NAc dopamine dynamics in male and female Long-Evans rats. Rats were separated into (n=15-16/group) 1) a control group fed a standard chow diet, 2) a group fed a high-fat diet, or 3) a group fed a low-fat/high-sugar diet for 12 weeks. At week 10, we found that the high-fat diet led to a significant decrease in preference for a high concentration of sucrose (12%) vs low concentration sucrose (4%) after 7 daily sessions. Next, all rats underwent stereotaxic surgery to inject the genetically encoded GPCR-activation-based-DA (GRABDA) and optical ferrules into the NAc and were switched to a standard chow diet. Rats underwent 15 days of Pavlovian conditioning where one cue predicted a sucrose pellet (CS+) and a different cue did not (CS-) to evaluate associative learning. We measured NAc dopamine dynamics on Day 1 and 15 of Pavlovian conditioning using fiber photometry. On Day 15, all groups discriminated between CS+ vs CS- as shown by increased time spent in the food cup (diet, cue type: p<0.0001) and increased entries into the food cup during the CS+ vs CS- (diet: p=0.02, cue type: p<0.0001), indicating preservation of learning mechanisms. Rats fed the high-fat spent less time in the food cup during both cues compared to standard chow rats, suggesting diminished motivated behavior. On Day 15, high-fat rats show abolished NAc dopamine dynamics to a reward-predictive cue compared to standard chow and low-fat/high-sugar rats. Taken together, a high-fat diet alters reward processing, motivated behavior, and NAc dopamine signaling.

3:15

Amygdala&Ndash;Liver Signaling Orchestrates Glycemic Responses To Stress
Jamie RE Carty¹, Kavya Devarakonda¹, Richard M Connor², Sarah A Stanley¹
¹Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ²Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States

Behavioural adaptations to environmental threats are crucial for survival and necessitate rapid deployment of energy reserves. The amygdala coordinates behavioural adaptations to threats, but little is known about its involvement in underpinning metabolic adaptations. Here we show that acute stress activates medial amygdala (MeA) neurons that innervate the ventromedial hypothalamus (MeAVMH neurons), which precipitates hyperglycaemia and hypophagia. The glycaemic actions of MeAVMH neurons occur independently of adrenal or pancreatic glucoregulatory hormones. Using whole-body virus tracing, we identify a polysynaptic connection from MeA to the liver that promotes the rapid synthesis of glucose by hepatic gluconeogenesis. Repeated stress exposure disrupts MeA control of blood glucose, resulting in diabetes-like dysregulation of glucose homeostasis. Our findings reveal an amygdala–liver axis that regulates rapid glycaemic adaptations to stress and links recurrent stress to metabolic dysfunction.

3:30

Branched-Chain Amino Acids Modulate Sweet Reward Independently Of Neuronal Fgf21 Signaling
Fereshteh Dehghani, Danial Fotros, Zobayda Farzana Haque, Garrett Scott, Maura McKenna, Andrew C Shin
Neurobiology of Nutrition Laboratory, Department of Nutritional Sciences, College of Health & Human Sciences, Texas Tech University, Lubbock, TX, United States

Higher branched-chain amino acid (BCAA) levels are linked to obesity.BCAA restriction stimulates fibroblast growth factor 21 (FGF21),which reduces sweet intake in mice.Whether BCAAs regulate reward through FGF21 remains unclear.We examined the effects of dietary,pharmacological,microbial BCAA manipulation,as well as the role of neuronal FGF21 signaling (Klb^ΔSynCre) on sucrose reward.36 male C57BL/6J mice received control,restricted,or supplemented BCAA diets for 3 months.48 mice fed a high-fat diet or regular chow for 12 weeks and received vehicle or BT2 (BCAA-lowering compound; 40 mg/kg ip) daily for 1 month.Another 48 mice fed a HF diet or chow for 8 weeks and received vehicle or BCAA-synthesizing bacterium Prevotella copri (5×10⁸, CFU/mouse) in the last 3 weeks.Klb^ΔSynCreand Klb^flox/flox mice underwent BCAA restriction for 12 weeks.Two-bottle choice,taste reactivity,and progressive ratio tests were performed to assess the hedonic impact (“liking”) and motivation (“wanting”).BCAA-supplemented mice showed 20% higher sucrose intake than control and restricted groups with greater liking and wanting for sucrose.In lean mice,BT2 reduced sucrose intake by 16% without affecting liking or wanting.HF-fed obese mice displayed less liking and wanting for sucrose than lean controls.BT2 did not alter sucrose intake or wanting in obese mice but restored sucrose liking impaired by HF diet. P.copri increased sucrose intake by 16% in lean mice,but tended to further reduce sucrose intake,liking,and wanting in obese mice.Klb^ΔSynCre mice did not alter food reward behaviors,indicating FGF21-independent BCAA effects.Lowering BCAA levels may reduce appetite and motivation for sweet stimulus,highlighting a novel role for BCAAs in food reward regulation.

3:45

Sweet Taste Phenotypes Are Poor Predictors Of Sugar Intake In Healthy Adults
Alissa Nolden, James Makame
University of Massachusetts, Amherst, MA, United States

Individual differences in sweet taste perception are widely assumed to influence sugar intake, yet evidence linking laboratory-derived sweet taste phenotypes to real-world dietary behavior remains inconsistent. Therefore, the objective of this study was to examine the relationship between sucrose-based sweet taste phenotypes, preferences for sweet foods, and dietary intake, specifically total sugar and energy intake. It is hypothesized that perceived intensity and liking of sucrose are associated with liking and intake of sweet foods and beverages. A total of 121 healthy adult participants (aged 18-46; 71.1% female; BMI 24.8±5.0) completed sensory testing and dietary assessments. Sweet taste perception and hedonic liking were evaluated using five sucrose solutions (0.16-0.73M). Intensity ratings were collected using a generalized Labelled Magnitude Scale, and liking was assessed using a generalized bipolar hedonic scale. Participants completed three types of assessments to gain insight into the liking and intake of sweet foods and beverages (24-hour recalls, FFQ, and behavioral assessments). Agglomerative hierarchical clustering of hedonic responses identified three stable sweet-taste phenotype groups based on the combination of reported liking and perceived intensity: low (n=22), medium (n=29), and high (n=63) sweet-liking groups. Contrary to our hypothesis, there was no relationship between sweet-taste phenotypes and total sugar or added sugar intake. However, a weak relationship was observed between sweet-taste phenotypes and self-reported liking of sweet foods and beverages (e.g., cotton candy). Together, these results challenge the translational utility of sweet taste phenotyping for predicting sugar intake among healthy adults.

4:00

Sglt1 Mediates Oral Glucose Sensitivity During Fasting In Humans
Alexa Pullicin, Yixin Jia, Juyun Lim
Monell Chemical Senses Center, Philadelphia, PA, United States

Oral glucose sensing is critical for maintaining energy homeostasis, particularly when the body is in an energy-seeking state. We previously showed that suprathreshold concentrations of glucose are perceived as relatively sweeter when fasted compared to fed, and that this effect does not extend to other sweet tastants. To investigate the peripheral mechanism underlying this phenomenon, we conducted a series of experiments. In each experiment, overnight fasted participants attended separate study sessions, and oral detection sensitivity to target compounds, with or without a modulator, was measured before and after consuming a standardized meal to satiety (295–1475 kcal). In the first experiment (N=27), we confirmed our initial finding by testing detection thresholds for glucose, fructose, and sucralose. Results showed that, on average, individuals had lower detection thresholds for glucose when fasted versus fed (paired t-tests; p <0.05), and this effect did not extend to fructose or sucralose. In the second experiment (N=24), we investigated the role of the sodium glucose co-transporter 1 (SGLT1), expressed in gustatory tissue, by measuring glucose detection thresholds under three conditions: 1) normal, 2) pharmacological inhibition of SGLT1 with sotagliflozin, and 3) SGLT1 enhancement with sodium chloride. As expected, under normal conditions, participants were more sensitive to glucose when fasted compared to fed (p = 0.01). This effect was abolished following oral pre-treatment with sotagliflozin (p > 0.05) and enhanced when NaCl was added to test solutions (p <0.01). These findings demonstrate that SGLT1 is involved in the increased oral sensitivity to glucose when fasted, revealing a mechanism by which the gustatory system contributes to metabolic homeostasis.

4:15

Brain Response Is Influenced By Varying Rates Of Metabolic Response To Carbohydrate Consumption In A Flavor-Nutrient Conditioning Paradigm
Mary E Baugh¹, Monica Ahrens², Han Lee¹, Rhianna Sullivan¹, Zach Hutelin^1,3, Alexandra DiFeliceantonio^1,4
¹Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, United States, ²Department of Internal Medicine, Division of Medical Informatics, University of Kansas Medical Center, Kansas City, KS, United States, ³Translational Biology, Medicine, and Health, Virginia Tech, Blacksburg, VA, United States, ⁴Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA, United States

Prior work highlights the sufficiency of post-ingestive glucose sensing to support learned carbohydrate preferences, but whether the rate of metabolism modulates reinforcing potential is unclear. We assessed if metabolic response rate is associated with brain response and behavioral preference in an ongoing randomized, crossover flavor-nutrient conditioning study. Participants aged 18-45y (n=23; target n=64) consumed iso-sweet, novelly flavored drinks containing no calories (sucralose; CS-), 110 kcal maltodextrin (CS+M), and 110 kcal sucrose (CS+S) 6 times each. Indirect calorimetry and blood draws were performed at baseline and for 1-hr post-consumption. Preliminary analyses indicate blood glucose area under the curve (AUC) was greater for CS+M than CS+S and CS-, and carbohydrate oxidation AUC was greater for CS+S than CS+M and CS- (all p<0.01). Pre-to-post liking and wanting ratings did not differ across conditions, nor did overall neural response (fMRI) across conditions to visual cues or flavor delivery (tested in extinction). There was an interaction between blood glucose AUC and condition in response evoked by the visual cue in the precuneus (F=29.72, p_FWE=0.003), driven by an attenuated response for CS+S vs CS- (t=7.71, p_FWE<0.001). Given the directional differences in metabolic response for CS+S and CS+M, we performed T contrasts consistent with these opposing metabolic profiles. Blood glucose AUC was associated with a greater cue-evoked response for CS+M>CS+S in the putamen and delivery-evoked response for CS+M>CS+S in the ventrolateral prefrontal cortex and nucleus accumbens (all t>5.6, SVC pFWE<0.02). These findings support the hypothesis that rate of metabolic response to carbohydrate consumption influences neural responses.

10:00

The Crunchometer: A Low-Cost, Open-Source Acoustic Analysis Of Feeding Microstructure
Ranier Gutierrez
CINVESTAV del IPN, Mexico City, Mexico

Elucidating the neuronal circuits that govern appetite requires a detailed analysis of the microstructure of solid food consumption. A significant barrier in this field is that existing techniques for monitoring feeding are either prohibitively expensive, limiting their use, or lack the high temporal resolution necessary to align feeding events with neuronal activity. To overcome this, we developed the Crunchometer, a low-cost, open-source acoustic system that uses computational algorithms to create high-resolution feeding ethograms. We validated the system by monitoring feeding across different energy states (hunger/satiety) and by demonstrating that the anti-obesity drug semaglutide suppresses food intake and reduces preference for a high-fat diet. Crucially, the Crunchometer integrates seamlessly with in vivo neural recordings in freely behaving mice. By pairing our system with electrophysiology in the Lateral Hypothalamus (LH), we identified novel “meal-related” neurons that track entire meals rather than individual feeding bouts. Using calcium imaging, we further revealed that solid food consumption strongly modulates LH GABAergic and glutamatergic neurons. We also found that distinct LH neuronal ensembles encode the consumption of solid food versus liquid sucrose. The Crunchometer is thus a powerful and accessible tool for precisely dissecting the neural correlates of naturalistic feeding behavior.

10:30

Doing More With Less: Open-Source Tools Reveal Hidden Structure In Feeding And Motivation
Bridget Matikainen-Ankney
Rutgers University, Piscataway, NJ, United States

Open-source behavioral tools are fundamentally reshaping how we study ingestive behavior. Tools like FED3, FORCE, and home-cage activity monitoring systems are making the field more accessible, and generating data sets that are flexible and rich. These tools offer simple and adaptable methods to measure food-seeking and effort-based behaviors in a variety of experimental contexts. Assays using FED3 and FORCE, in particular, have been valuable for investigating motivated behaviors in mouse models of diet-induced obesity and weight loss. These platforms enable rapid data collection and efficiently allow iterative experimentation, which is particularly beneficial when establishing a research program. Another key strength of these tools is their ability to produce datasets that extend far beyond their initial applications. For instance, operant feeding assays with FED3 do more than track responses within a reinforcement schedule; they also capture the daily rhythms of feeding. Similarly, home-cage activity monitoring continuously records locomotion, which can then be analyzed alongside food-seeking behavior to uncover time-specific behavioral patterns that escape detection in traditional assays. The resulting datasets are complex, and can be mined again and again as new research questions arise. And while such rich datasets once posed analytical challenges, recent advances in analytical tools, especially those leveraging artificial intelligence, are breaking down such barriers, making sophisticated analyses accessible to all researchers, especially trainees. In sum, open-source tools are broadening access to behavioral neuroscience and enabling new lines of inquiry into feeding and motivation.

11:00

Ingestion On A Budget: Digital Mealtime Photography For Scalable Eating Behavior Assessment
Laura L Bellows
Cornell University, Ithaca, NY, United States

Measuring eating behaviors is often expensive, staff-intensive, and disconnected from real-world contexts, limiting scalability, particularly in low-resource populations. Digital food photography offers a cost-effective alternative that captures eating behaviors where they actually occur: at home. Prior work using the Remote Food Photography Method demonstrated feasibility among low-resource families, with 85% of expected dinner meal images captured and yielding rich contextual data on meal timing, preparation, and quality. Similarly, food photography in child care settings has enabled objective assessment of foods offered and consumed, revealing persistent gaps in diet quality (e.g., only 16% of packed lunches meeting nutrition guidelines) while reducing reliance on direct observation. Building on this foundation, we developed a mobile app–based mealtime photography tool that enables parents to capture before-and-after images of their child’s meals in real time. This approach reduces participant burden while generating objective data on foods offered, intake, and meal quality in the home environment. Pilot data demonstrate strong feasibility and engagement with repeated photo capture, supporting its use as a scalable assessment strategy. By shifting data collection from researchers to caregivers, digital food photography transforms assessment into a low-cost, scalable tool that can also support intervention delivery. This approach offers a practical pathway to expand access to behavioral nutrition interventions in resource-constrained settings and provides new insight into the context of eating behaviors beyond intake alone.

10:00

A Homecage Social Operant Task To Investigate Diet-Induced Changes In Social Motivation
Yiru Chen, Susan E. Maloney, Alexxai V. Kravitz
Washington University in St. Louis, St. Louis, MO, United States

Obesity and high-fat diet (HFD) consumption alter reward-related neural circuits, including dopaminergic signaling, which is critical for motivated behaviors. While metabolic consequences of HFD are well characterized, less is known about how these diets influence social motivation, a key domain disrupted in several neuropsychiatric conditions. We hypothesize that chronic HFD impairs social motivation in mice through disruption of dopamine signaling. To test this, adult C57BL/6J mice (both sexes) were assessed using a homecage social operant paradigm developed in our laboratory that enabled continuous, low-stress measurement of social motivation across days. In this task, mice performed a nose-poke to open an automated door granting access to a conspecific, allowing quantification of social-seeking behavior and its circadian rhythms. Our previous work found that a social partner increased social-seeking behavior, which could be reduced by dopamine antagonists. Mice maintained on standard chow or HFD were assessed for social operant responding across the circadian cycle, while dopaminergic activity was concurrently measured using fiber photometry to determine how diet-induced changes in metabolic state affect neural encoding of social reward. This approach enabled simultaneous assessment of feeding manipulation, neural activity, and social behavior in an ethologically relevant context. These findings provide insight into how diet-induced metabolic dysfunction impacts social motivation and its neural substrates, advancing understanding of interactions between energy balance, dopamine signaling, and social behavior.

10:15

Circuit-Specific Effects Of Post-Ingestive Modulation Of Dopamine In Food Reward
Tung T Bui¹, Bhaskar Ray², Brandon Cox¹, Alec Hartle¹, Alexandria Difeliceantonio¹, Srijan Sengupta², William M Howe¹
¹Virginia Polytechnic Institute & State University, Blacksburg, VA, United States, ²North Carolina State University, Raleigh, NC, United States

Post-ingestive signals triggered by gut nutrient sensors contribute to food reward in part by affecting dopamine (DA) release dynamics in the striatum. However, the spatial and temporal signatures of these post-ingestive effects, and their causal contributions to different components of food reward are less clear. Here, we conducted a series of experiments to test the hypothesis that temporally and spatially specific effects on striatal DA release enable post-ingestive signals to mediate both the attractiveness of food rewards, as well as food cue-reward learning. In the first study, we implanted intragastric (iG) catheters in C57 mice to measure the influence of post-ingestive signals triggered by different macronutrients (lipids, sucrose, combination, or PBS) on DA release in the dorsal striatum (DS, n=7) and nucleus accumbens (NAc, n=8). We found that these infusions selectively modulated the amplitude of spontaneous DA in the DS, and that this effect peaked 10-20 minutes after nutrient infusion. To assess the causal role of these effects on food choice, channelrhodopsin was expressed in the DA neurons of SNc of DAT-Cre mice (N=10). We found that amplifying DA release selectively during this time window of peak post-ingestive effects was sufficient to increase preference for a previously non-preferred macronutrient. Finally, in a separate cohort of mice (n=13) we show that post-ingestive signals triggered by iG macronutrient infusions were sufficient to support the temporal shift of DA to reward-predictive cues in the NAc, but not the DS. Our combined data support a model whereby post-ingestive modulation of DS vs NAc DA release are necessary and sufficient to support food preference, and food cue-reward learning, respectively.

10:30

Prefrontal&Ndash;Hypothalamic Dynamics During Binge-Like Eating: Feeding Microstructure And In Vivo Neural Activity During Palatable Food Consumption
Astrid Munoz-Perez de Arce¹, Pablo R. Moya^2,3, Ignacio Negron-Oyarzo²
¹PhD Program in Sciences (Neuroscience), Faculty of Sciences, Universidad de Valparaiso, Valparaiso, Chile, ²Institute of Physiology, Faculty of Sciences, Universidad de Valparaiso., Valparaiso, Chile, ³Centro Interdisciplinario de Neurociencias (CINV), Universidad de Valparaiso, Valparaiso, Chile

Binge eating (BE) is characterized by the rapid consumption of palatable food (PF), reflecting impaired cognitive control over feeding behavior. The lateral hypothalamus (LH) regulates consummatory processes, while the medial prefrontal cortex (mPFC) contributes to inhibitory control. However, whether mPFC–LH communication is altered during binge-like feeding behavior remains unknown. We hypothesize that binge-like feeding is associated with impaired mPFC–LH coupling during PF consumption. To test this, adult female C57BL/6 mice were subjected to intermittent access to PF for 4 weeks to induce BE. Simultaneous in vivo electrophysiological recordings (local field potentials and single-unit activity) were obtained from the mPFC and LH during feeding sessions. Binge animals exhibited a time-dependent increase in feeding bursts compared to controls (n = 7 per group, p <0.05), primarily concentrated within the first 15 minutes of the session, indicating temporally clustered intake. Preliminary analyses suggest reduced firing rates in the mPFC, but not in the LH, during PF consumption events in binge animals at Week 4 (mPFC: 91 vs 67 units; LH: 46 vs 45 units, binge vs control; recordings from 2 animals per group), indicating region-specific alterations in neural activity. These findings indicate region-specific neural alterations associated with binge-like feeding. Ongoing analyses will determine how prefrontal–hypothalamic dynamics contribute to dysregulated feeding and loss of control, providing insight into circuit mechanisms underlying disordered eating.

10:45

Differences In The Propensity To Attribute Incentivization Of Food Cues Is Reflected In The Calcium Activity Of Anterior Insular Cortical Neurons
Keegan H Delap, Kajol V Sontate, Gregory C Loney
Department of Psychology, Program in Behavioral Neuroscience, SUNY University at Buffalo, Buffalo, NY, United States

A contributing factor to obesity is preoccupation with food-related stimuli often termed “food noise”. Individual variation in reactivity to food cues underlies food noise and contributes to difficulty in maintaining a healthy diet. In both humans and rodents, individual differences in the attribution of incentive salience to food cues is associated with overeating and weight gain. Specifically, some individuals incentivize food-predictive cues (sign-trackers) while others maintain incentivization of the outcome (goal-trackers). The mechanisms underlying these differences are unknown. Insular cortex (IC) is critical for forming associations between exteroceptive stimuli and interoceptive states and thus IC neural activity may explain differences in food-cue reactivity. Here, we expressed GCaMP6s in the anterior IC of rats to permit visualization of calcium activity in this neuronal population. Next, rats were trained on a Pavlovian conditioned approach paradigm for 7 days. IC photometry recordings were obtained and situated around behaviorally relevant events (i.e. cue delivery and food consumption). We found a significant day x phenotype interaction (F(2, 14) = 3.976, p <.05) as the neural response to the cue in sign-trackers was significantly higher than goal-trackers post-conditioning. Post-hoc analyses revealed that sign-trackers differed in their response to the cue from day 1 to day 7 (p <.01) while goal-trackers did not (p = 0.93). These data support that neural processing of cues within IC may explain phenotypic differences in cue reactivity. Future studies will determine if manipulating IC neural activity during cue presentations alters cue reactivity and whether administration of GLP-1 agonists reduce the neural response to food cues in sign-tracking rats.

11:00

A Pedunculopontine Nucleus To Ventral Tegmental Area Circuit Is Required For Dopamine Responses To Food And Associative Food-Cue Learning
Nicholas Smith¹, Ruoxi Wu¹, James Bianchi¹, Albert Yeung¹, Semus Wang¹, Michelle Awh¹, Sukya Williams¹, J. Nicholas Betley^1,2,3
¹Department of Biology, Universtiy of Pennsylvania, Philadelphia, PA, United States, ²Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, ³BrainBodyBiome Center, University of Pennsylvania, Philadelphia, PA, United States

The modern food environment is brimming with advertisements, packaging, and contexts that powerfully drive consumption. As we associate these cues with the palatable and rewarding food that they predict, the cues themselves gain motivating power over our eating decisions. However, the neural circuits that shape associative learning for food cues are incompletely understood. We hypothesized that excitatory input to the dopamine system mediates the communication of cue and food reward information, enabling associative learning that ascribes appetitive drive to food cues. Here, we demonstrate in mice that the pedunculopontine nucleus (PPN) to ventral tegmental area (VTA) circuit is required for phasic dopamine release across the brain in both the nucleus accumbens and the basolateral amygdala. Inhibiting the PPN to VTA circuit causes significant deficits in both appetitive Pavlovian conditioning and fear conditioning, without impairments in instrumental learning or food motivation. Using endoscopic calcium imaging, we found that hunger increased the proportion of PPN cells responding to food, whereas satiety hormones suppress neural activity in the PPN. Furthermore, we identify synaptic and intrinsic electrophysiological mechanisms that support increased excitation of the PPN during hunger. Finally, we use spatial transcriptomics to parse apart genetically defined cell clusters in the PPN with distinct functional roles. Together, these findings describe the PPN to VTA circuit as essential in the neural architecture for food reward, enabling food to project dopamine across the brain and support associative learning. Therapeutically targeting this pathway could alter the motivational impact of eating and limit the ability of food cues to tempt unhealthy eating.

11:15

Lateral Hypothalamic Circuits Integrate Threat And Food Value To Drive Compulsive Eating In Obese Mice
Richard O'Connor, Paul Kenny
Icahn School of Medicine/Mount Sina, New York, NY, United States

We investigated how the hypothalamus-habenula circuit influences foraging behavior and its connection to obesity. Through in vivo calcium imaging in mice, we discovered that neurons in the lateral habenula (LHb) respond to food detection in ways shaped by the level of environmental threat. As mice gain weight, these LHb responses change, so even in hazardous situations, palatable food produces “value signals” similar to those seen during starvation. Consequently, mice with diet-induced obesity fail to adapt their feeding behavior, continuing to consume palatable food even in environments associated with aversive footshock or in the presence of an innately aversive stimulus, such as TMT. Using ex vivo electrophysiology, we found that lateral hypothalamic (LH) glutamatergic neurons projecting to the habenula were hyperpolarized in obese animals. Employing the FOS-Cre TRAP system, we selectively expressed inhibitory hM4Di DREADD in LH neurons activated by TMT exposure. Administration of the DREADD ligand CNO prevented animals from reducing food intake during subsequent exposures to TMT or environments associated with aversive footshock. We observed similar disruptions in adaptive behaviors when we directly inhibited activity in the LHb or virally lesioned excitatory input to the LHb. Thus, inhibiting threat-responsive neurons in the LH and their connections to the LHb resulted in compulsive feeding that failed to adjust to threatening stimuli. Notably, these behaviors mirrored those seen in mice that became obese after extended access to highly palatable foods. We propose that LH glutamatergic neurons, via projections to the LHb, link food value to risk tolerance, and shifts in these habenular value signals precipitate compulsive eating in obesity.

1:00

Assessment And Modification Of Ingestive Behavior As A Multi-Component Construct: Selecting The Best Method For The Population And Variable Of Interest
Corby Martin
Pennington Biomedical Research Center, Baton Rouge, , United States

Ingestive behavior is a multi-component construct encompassing several distinct behaviors and variables of interest. Various methods exist to assess ingestive behavior and these methods vary widely on their approach; assumptions; participant, researcher, or clinician burden; and incorporation of technology. Moreover, the validity of these methods varies widely, yet the validation data is not always consistent over different populations, endpoints of interest, or the state of participant (e.g., weight stable vs. weight unstable). This can result in selecting and using a dietary assessments method that is not suited for the variable of interest or the target population. These risks can be minimized, however, if we gain a better understanding of which aspect of ingestive behavior is the most relevant study or clinical outcome, and which methods are empirically supported to assess those outcomes in the population of interest. These issues will be reviewed during this talk and will include a critical review of assessing dietary and energy intake across the lifespan using a wide range of assessment methods, in addition to assessing meal frequency and meal timing via passive technology. Attendees will gain a better understanding of the strengths and weaknesses of dietary assessment methods based on what aspect of ingestive behavior is of interest and among which populations. Further, the review of assessment methods will include their ability to support modification of ingestive behaviors, including what and how much food is consumed, and when eating occurs. � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��

5:00 - 6:30 PM	Millennium Hall
Opening Reception & Exhibits

9:00 - 10:00 AM	Millennium Hall
Poster Session 1, Exhibits & Coffee Break

12:00 - 1:30 PM	Room 1
Oral Session 1: Oh Behave! Understanding Ingestive Behavior

12:00 - 1:30 PM	Room 2
Oral Session 2: Circuit City: Connections in Ingestive Behavior

3:00 - 4:30 PM	Room 2
Symposium 1: You even eat protein, bro?

3:00 - 4:30 PM	Room 1
Oral Session 3: From Milk to Meals: Early Life & Child Eating Behavior

4:30 - 5:30 PM	Millennium Hall
Poster Session 2, Exhibits & Coffee Break

9:00 - 10:00 AM	Millennium Hall
Poster Session 3, Exhibits & Coffee Break

10:00 - 11:30 AM	Room 2
Symposium 2: Boldly Going: The next generation in testing neuromodulators

10:00 - 11:30 AM	Room 1
Oral Session 4: K-Pop Diet Hunters: Diet Quality & Health

1:30 - 3:00 PM	On Own
Lunch on Own

9:00 - 10:00 AM	Millennium Hall
Poster Session 4, Exhibits & Coffee Break

10:00 - 11:30 AM	Room 1
Oral Session 5: Pour Some Sugar on Me: Carbohydrates & Sugar

10:00 - 11:30 AM	Room 2
Oral Session 6: Molecules that Matter: Neuropeptides & Feeding

2:00 - 3:00 PM	Millennium Hall
Poster Session 5, Exhibits & Coffee Break

3:00 - 4:30 PM	Room 2
Symposium 3: Gut Check: Mechanosensory signals in satiation

3:00 - 4:30 PM	Room 1
Oral Session 7: Ch-Ch-Ch-Ch-Changes: Interventions & Therapeutics

9:00 - 10:00 AM	Millennium Hall
Poster Session 6, Exhibits & Coffee Break

10:00 - 11:30 AM	Room 2
Symposium 4: Ingestion on a Budget

10:00 - 11:30 AM	Room 1
Oral Session 8: The 8th Sense: Interoception and Appetite

6:30 - 10:30 PM	Millennium Hall
Awards Ceremony & Closing Banquet