Abstract Disclosure: J. Tong: None. Y. Heianza: None. E.A. Schur: None. F. Sacks: None. L. Qi: None. E.J. Boyko: None. Weight loss maintenance is a challenging problem commonly encountered in obesity management. The biological mechanism for weight regain following diet-induced weight loss is not well understood. The orexigenic gut hormone ghrelin increases appetite and food intake and promote positive energy balance. We aim to investigate whether weight-loss induced fasting ghrelin changes predict subsequent weight regain in the POUNDS LOST trial. Methods: This study included 244 overweight or obese adults (age: 52.9±8.8 yr; 66% female; BMI 32.4±3.9 kg/m2 [mean ± SD]) randomly assigned to 1 of 4 weight-loss diets varying in macronutrient intake who had fasting plasma total ghrelin levels measured at baseline, 6 and 24 months after the intervention. We examined associations between fasting ghrelin levels changes between baseline and 6-months (weight change: -7.1±5.3 kg) and body weight change between 12 and 24 months (3.2±3.9 kg). Results: Fasting plasma ghrelin level increased significantly at 6 months (from 487.3±251.1 to 574.0±274.5 pg/mL) and remained elevated at 24 months despite weight regain (684.0±411.0 pg/mL). Increases in ghrelin level from baseline to 6 months (86.7±167.4 pg/mL) were correlated with weight regain from 12 to 24 months (p=0.018). The association was unchanged after adjustment for age, sex, race, and diet assignment at baseline; fat and carbohydrate craving scores, hunger and fullness ratings, dietary restraint and disinhibition scores measured at 6 months, prior to onset of weight regain. Conclusions: Fasting ghrelin levels rose in response to diet-induced weight loss and persisted for 2 years despite weight regain. Ghrelin change during the weight loss phase predicts subsequent weight regain independent of appetite and craving measures. Understanding the mechanistic connection between ghrelin action and weight regain may shed light on novel approaches to weight loss maintenance. Presentation: Friday, June 16, 2023
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