Physiological and behavioral phenotyping to predict responsiveness to lifestyle interventions in obesity: toward individualized strategies for weight-loss maintenance.

Obesity treatment is marked by substantial interindividual variability in weight-loss response and long-term maintenance. This project aims to investigate whether enteroendocrine, metabolic, and appetite-related responses to a mixed-meal tolerance test (MMTT) predict weight loss and its maintenance in adults with overweight or obesity undergoing a 36-week lifestyle intervention. Men and women aged 20-55 yrs, with BMI of 28-40 kg/m² (n=120) will be assessed at baseline and post-intervention (36 weeks) for body mass and body composition and will undergo an MMTT for the assessment of postprandial gut hormones, glucose, insulin, appetite perceptions, and state food craving. In a subsample, metabolic flexibility and free-living total daily energy expenditure (doubly labelled water) will be measured as exploratory variables. At follow-up (36-48 weeks after the end of intervention), body mass and body composition will be assessed. Weight-loss response will be quantified as the percentage of body weight loss from baseline to post-intervention, and maintenance will be analyzed as body mass change from post-intervention to follow-up. Multiple linear regression models will be used to test whether baseline postprandial enteroendocrine hormone responses predict weight loss, while secondary and exploratory analyses will examine appetite-related, glycemic, insulin, metabolic, and energy expenditure variables. Additional biological and behavioral variables will be considered as covariates or exploratory predictors when appropriate. This project is expected to help identify physiological and behavioral profiles associated with high or low responsiveness to lifestyle interventions and to inform future individualized strategies for obesity care. Beyond its scientific aims, this project will consolidate an independent research line at UNICAMP focused on physiological and behavioral predictors of responsiveness to lifestyle interventions in obesity. It will also strengthen human resource training, international collaborations, and the development of a research platform for less stigmatizing obesity care.