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Objective Although aging is associated with reduced hunger and energy intake (EI), obesity is increasing in older adults. This study aimed to identify appetite regulation differences between older adults with obesity and older adults with normal weight (NW). Methods This cross‐sectional study recruited older adults with obesity (BMI 30–40 kg/m2) and NW (BMI < 25 kg/m2) aged 65–85 years. Fasting appetite‐related behavioral questionnaires were collected. Ghrelin, polypeptide YY [PYY], glucagon‐like peptide‐1 [GLP‐1], glucose, insulin, and triglycerides were measured fasting and every 30 min for 3 h following a test breakfast, and the incremental area under the curve (iAUC) was calculated. Results 13 older adults with obesity (aged 70.8 ± 4.0 years, 54% female, BMI 33.1 ± 3.6 kg/m2) and 14 with NW (aged 70.8 ± 5.3 years, 71% female, BMI 22.5 ± 2.1 kg/m2) were analyzed. Compared to older adults with NW, older adults with obesity had higher disinhibition and perceived hunger (p < 0.001 and p < 0.05, respectively), lower confidence in preventing overeating (p < 0.05), higher fasting GLP‐1 and insulin (both p < 0.05), and higher PYY and insulin iAUCs (p < 0.01 and p < 0.05, respectively). Conclusion Despite similar meal‐related appetite and EI, older adults with obesity had higher fasting disinhibition, perceived hunger, GLP‐1 and insulin, higher PYY and insulin iAUCs, and lower confidence in preventing overeating than those with NW. These differences between older adults with obesity and NW have implications for tailored obesity treatments in older adults. Aging can be associated with anorexia and weight loss, but obesity is also increasing among older adults. Compared to older adults with normal weight (n = 14, red line), older adults with obesity (n = 13, blue line) had (1) altered eating‐related behaviors, including higher disinhibition and perceived hunger and lower confidence in preventing overeating, (2) differences in appetite‐related hormones, including higher fasting glucagon‐like peptide‐1 and polypeptide YY meal response, and (3) greater insulin resistance. These differences in appetite‐related behaviors and peptides have implications for tailored obesity treatments in older adults.

Abstract Disclosure: J. Taormina: None. M. Bolt: None. M. Cornier: None. K.L. Moreau: None. M.E. Wierman: None. M.S. Rothman: None. K.T. Legget: None. J.R. Tregellas: None. A.K. Hild: None. D.B. Hammond: None. A. Gebregzabheir: None. M.P. Mancuso: None. M.D. Sammel: None. S.J. Iwamoto: None. Introduction: Plasma ghrelin is central to homeostatic control of hunger and is inversely correlated with total body weight and body fat percentage (BF%). Cisgender (cis) women have higher plasma ghrelin than cis men, and ghrelin is positively associated with serum estradiol in cis women and testosterone in cis men. Estradiol-based gender-affirming hormone therapy (GAHT) use in transgender (trans) women and testosterone-based GAHT use in trans men are associated with body weight increases and differential body composition changes. The association of GAHT with fasting total ghrelin and hunger in trans adults is understudied and may suggest one mechanism for weight and body composition changes observed with GAHT. Specific aim: To evaluate differences in fasting total ghrelin and hunger in adults across sex and gender. Hypothesis: Fasting total ghrelin and hunger are more similar by sex than by gender. Methods: Nonsmoking trans adults on GAHT for >1 year (no gonadectomy) and cis adults (no hypogonadism) participated in a cross-sectional study with fasting total ghrelin and insulin measurements, appetite-related questionnaires (visual analog scale [VAS] for hunger and satiety; Food Cravings Questionnaire-State Version [FCQ-S]), and dual-energy x-ray absorptiometry to measure BF%, after an overnight fast. Multivariable linear regression models examined differences between groups while adjusting for pre-specified covariates (age, BF%, fasting insulin). Results: Among 110 mostly white, non-Hispanic adults (48 cis women, 12 cis men, 34 trans women, 16 trans men), mean (±SD) ages were 39 (10), 39 (10), 44 (17) and 30 (8) years; mean BF% were 43 (4), 30 (4), 35 (8) and 30 (7) %; and mean fasting insulin levels (reference 0-20 uIU/mL) were 15 (7), 18 (9), 6 (4) and 4 (3) uIU/mL, respectively. In regression modeling, fasting total ghrelin was different in trans women (by -341.7 pg/mL, 95% CI [-520.1, -163.3], p < 0.001) and cis men (by -306.0 pg/mL, 95% CI: [-561.1, -51.0], p = 0.02) compared to cis women. Trans women, trans men, and cis men had similar ghrelin levels. Hunger VAS was different for all groups compared to cis women (trans men by -17.9 mm, 95% CI: [-34.9, -0.9], p = 0.04; trans women by -25.9 mm, 95% CI: [-38.3, -13.4], p < 0.001; cis men by -21.5 mm, 95% CI: [-39.4, -3.6], p = 0.02). Trans women, trans men and cis men had similar hunger VAS. Trans and cis adults scored similarly on satiety VAS and FCQ-S. Conclusions: Among trans women, lower fasting total ghrelin and hunger compared to cis women may be attributed to sex recorded at birth rather than estradiol-based GAHT use. Testosterone-based GAHT use may decrease hunger behavior but not fasting total ghrelin compared to pre-GAHT baseline. Future prospective studies can elucidate the impacts of sex recorded at birth, gender, and sex hormones on these and other hormonal and behavioral factors responsible for appetite regulation. Presentation: Sunday, July 13, 2025

Although sex differences in food intake have been observed consistently, contributing factors are not well understood. Using a cross-sectional online survey (n = 306; 151 men, 155 women), this study aimed to assess how sex impacts relationships between food ratings (appeal/desire to eat for high-calorie (HC) and low-calorie (LC) food images) and eating-related attitudes/behaviors, body mass index (BMI), and mood. Across participants, increased state- and trait-based hunger, disinhibition, and cravings were associated with both increased HC appeal and desire (p < 0.001). Increased state-based hunger and cravings were associated with greater LC desire (p < 0.001). Greater satiety was associated with decreased desire for both HC and LC (p < 0.001), while greater anxiety was associated with increased desire for both HC and LC (p < 0.001). Significant associations between BMI and food ratings were not observed. Women reported greater dietary restraint, trait-based hunger, disinhibition, eating disorder-related behaviors, depression, and stress compared to men, in addition to greater appeal and familiarity with LC foods (all p < 0.05). Significant effects of sex on the associations between food ratings and eating-related attitudes/behaviors, BMI, and mood were not observed, however. Findings support the importance of considering mood and eating-related attitudes/behaviors in investigations of food cue responsivity.