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Differential mechanisms affecting weight loss and weight loss maintenance

Abstract

In most lifestyle, pharmacological and surgical interventions, weight loss occurs over an approximately 6- to 9-month period and is followed by a weight plateau and then weight regain. Overall, only about 15% of individuals can sustain a 10% or greater non-surgical, non-pharmacological, weight loss. A key question is the degree to which the genotypes, phenotypes and environmental correlates of success in weight loss and weight loss maintenance are continuous or dichotomous. This Perspective is a comparison of the interactions of weight loss and maintenance with genetic, behavioural, physiological and environmental homeostatic systems and a discussion of the implications of these findings for research in, and treatment of, obesity. Data suggest that weight loss and weight loss maintenance are physiologically and psychologically different in many ways. Consequently, individuals may require different interventions designed for temporarily sustaining a negative energy balance during weight loss versus permanently maintaining energy balance after weight loss.

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Fig. 1: Schematic of the multiple systems that favour weight regain after successful weight reduction based on long-term inpatient studies4,27,100,101,102,103,104.
Fig. 2: Smoothed temporal changes in absolute weight or percentage weight in non-surgical, surgical, dietary, exercise and pharmacological interventions over time.

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Acknowledgements

These studies were supported, in part, by grants from the National Institutes of Health (UL1 TR00040 to M.R.), the National Institute of Diabetes and Digestive and Kidney Diseases (R01 30583 and R01 64773 to M.R., R01 DK130851 to G.F.) and the National Heart, Lung, and Blood Institute (1UG3 H163121 to G.F.).

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Rosenbaum, M., Foster, G. Differential mechanisms affecting weight loss and weight loss maintenance. Nat Metab 5, 1266–1274 (2023). https://doi.org/10.1038/s42255-023-00864-1

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