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Obesity-induced and weight-loss-induced physiological factors affecting weight regain

Nature Reviews Endocrinology volume 19, pages 655–670 (2023)Cite this article

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Abstract

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.

Key points

  • Weight regain after diet-induced weight loss is a common phenomenon and probably involves physiological mechanisms.

  • Studies in the past decade suggest the existence of an obesity memory with respect to adipose tissue inflammatory cell populations and metabolic changes, which might have a role in weight regain.

  • The role of persistent changes in appetite-related factors in weight regain and the interaction of these factors with the brain needs further study.

  • Strategies to reduce weight regain after weigh loss (diet composition, exercise, pharmacotherapy and other biomedical applications) should be considered.

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Fig. 1: Potential mechanism for the influence of macrophages on obesity development and on weight regain after weight loss.
Fig. 2: The physiology of weight regain.

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    Marleen A. van Baak & Edwin C. M. Mariman

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van Baak, M.A., Mariman, E.C.M. Obesity-induced and weight-loss-induced physiological factors affecting weight regain. Nat Rev Endocrinol 19, 655–670 (2023). https://doi.org/10.1038/s41574-023-00887-4

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