Why weight loss is difficult for some people, easier for others and often temporary remains one of the most debated questions in nutrition and metabolism. A new review suggests part of the answer may lie in how the body regulates weight in the first place.
Researchers at the Pennington Biomedical Research Center reviewed decades of human research to examine two leading models of body weight regulation: the traditional “set point” theory and a newer “dual-intervention point” model. Their analysis was published in Nature Reviews Endocrinology.
The set point model proposes that each person has a biologically determined target weight. When body weight rises above or falls below that point, the body responds by adjusting appetite, energy expenditure or both to restore the original weight.
The dual-intervention point model offers a different explanation. Instead of defending a single weight, the body may operate within an upper and lower range. Within that range, weight is shaped largely by environment and behavior. Biological defenses are triggered only when weight drops below the lower boundary or rises above the upper boundary.
“Human body weight appears to be regulated by biological mechanisms we still do not fully understand,” said Eric Ravussin, Boyd Professor and Douglas L. Gordon Chair in Diabetes and Metabolism at Pennington Biomedical. “Our analysis highlights the need to rigorously test state-of-the-art technology whether humans defend a single biologically determined set point or whether they operate within upper and lower intervention boundaries.”
The distinction matters because the two models predict different biological responses to prolonged dieting or overfeeding. Under the dual-intervention model, strong metabolic defenses against weight loss may coexist with relatively weak defenses against gradual weight gain, particularly in modern food environments.
The authors suggest this framework may help explain several long-observed patterns: why some people regain weight quickly after dieting, why others remain lean without apparent effort, why some individuals remain underweight despite abundant food and why body weight tends to increase slowly with age.
The review also emphasizes that it remains unclear what the body is ultimately trying to protect, whether fat mass, muscle mass, energy reserves or cellular energy balance. Untangling these mechanisms will require carefully designed human studies that examine how metabolism, appetite and energy use respond to controlled changes in intake and expenditure.
“This analysis offers a useful framework for examining how biological and environmental factors interact to influence body weight,” said Jennifer Rood, interim senior vice chancellor and executive director of Pennington Biomedical. “By comparing set point and dual-intervention models, the research contributes to a clearer understanding of weight stability and weight change.”
The authors stress that neither model should be interpreted as destiny. Environment, diet, physical activity and social factors still play a major role, particularly within the defended weight range. Rather than offering a prescription, the review provides a framework for future research aimed at understanding why bodies respond differently to the same interventions.
This work was supported by a grant from Chile’s National Agency for Research and Development (FONDECYT) and by a U.S. National Institutes of Health–funded NORC Center Grant focused on nutrition and metabolic health across the lifespan.