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.
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