Mechanisms of weight regain after weight loss — the role of adipose tissue

Abstract

One of the biggest challenges in the management of obesity is the prevention of weight regain after successful weight loss. Weight regain after weight loss has large interindividual variation. Although many factors probably contribute to this variation, we hypothesize that variability in biological responses associated with weight loss-induced shrinking of subcutaneous adipocytes has an important role. In this Review, we show that weight loss-induced variations in cellular stress, extracellular matrix remodelling, inflammatory responses, adipokine secretion and lipolysis seem to be associated with the amount of weight that is regained after successful weight loss. Weight regain could therefore, at least in part, depend on a combination of these factors. Further research on the causality of these associations could aid the development of effective strategies to prevent weight regain after successful weight loss.

Key points

  • Weight regain after successful weight loss is a major problem for many individuals, and many factors are probably involved in driving weight regain.

  • Loss of fat mass induces shrinkage of adipocytes, which is accompanied by cell stress, inflammation, altered adipokine secretion and reduced lipolysis.

  • In the absence of extracellular matrix remodelling during adipocyte shrinkage, mechanical stress builds up between the cell and the oversized extracellular matrix, which inhibits lipolysis and the release of fatty acids from adipocytes.

  • Weight loss induces an inflammatory response in adipose tissue.

  • Evidence for the involvement of epigenetic modifications, in particular microRNAs, in weight regain is sparse.

  • Knowledge of weight regain after weight loss is mainly based on associations, and so research into the causality of such associated factors is needed.

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Fig. 1: Potential adipose tissue-related mechanisms involved in weight regain after weight loss.
Fig. 2: Adipocyte diameter distribution in different phases of weight loss and weight regain.
Fig. 3: Model of resolution of weight loss-induced adipocyte stress.
Fig. 4: Structure of the focal adhesion as the centre for mechanical stress.
Fig. 5: Working model for the role of weight loss-induced changes in adipose tissue in weight regain.

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Glossary

Energy balance

The balance between energy intake and energy expenditure.

Fasting fatty acid rate of appearance

The rate of release of fattyacids into the plasma in thefasting state, which can bedetermined by measuring thedilution of an infused fatty acidtracer in plasma.

Weight cycling

The repeated loss and regain of body weight.

Bayesian analysis

A statistical paradigm that answers research questions about unknown parameters using probability statements.

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van Baak, M.A., Mariman, E.C.M. Mechanisms of weight regain after weight loss — the role of adipose tissue. Nat Rev Endocrinol 15, 274–287 (2019). https://doi.org/10.1038/s41574-018-0148-4

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