Weight regain after successful weight loss resulting from lifestyle interventions is a major challenge in the management of overweight and obesity. Knowledge of the causal mechanisms for weight regain can help researchers and clinicians to find effective strategies to tackle weight regain and reduce obesity-associated metabolic and cardiovascular complications. This Review summarizes the current understanding of a number of potential physiological mechanisms underlying weight regain after weight loss, including: the role of adipose tissue immune cells; hormonal and neuronal factors affecting hunger, satiety and reward; resting energy expenditure and adaptive thermogenesis; and lipid metabolism (lipolysis and lipid oxidation). We describe and discuss obesity-associated changes in these mechanisms, their persistence during weight loss and weight regain and their association with weight regain. Interventions to prevent or limit weight regain based on these factors, such as diet, exercise, pharmacotherapy and biomedical strategies, and current knowledge on the effectiveness of these interventions are also reviewed.
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