OnDemand: June 2025 Grand Rounds - Studies of Overfeeding: Lessons for Body Weight Regulation-Studies of overfeeding: Lessons for body weight regulation

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Professor Bessesen discussed how overfeeding studies have shaped our understanding of body weight regulation. He argued that the body actively defends weight through coordinated changes in appetite, energy expenditure, physical activity, and metabolism, and that these responses occur not only with weight loss but also with overfeeding. Classic human and animal studies showed that forced overfeeding often leads to temporary weight gain followed by reduced spontaneous food intake and, in some cases, increased energy expenditure or physical activity, returning weight toward a regulated trajectory. Genetic differences strongly influence how individuals respond to overfeeding.  <br /><br />He emphasized that weight regulation may occur over days rather than single meals, and may involve a balance between fed and fasted states rather than a fixed “set point.” Short-term overfeeding experiments in humans and rats suggest that responses in fat oxidation, energy expenditure, and activity predict later weight gain.  <br /><br />Bessesen also linked these findings to modern anti-obesity medications such as tirzepatide, suggesting they may work partly by resetting this regulatory system rather than simply suppressing appetite. He concluded that better understanding of weight biology could lead to more rational obesity treatment, similar to how physiology guides therapy in hypertension.

Keywords

overfeeding studies

body weight regulation

energy expenditure

appetite control

physical activity

metabolism

obesity treatment

tirzepatide

weight gain prediction