Biological mechanisms that promote weight regain following weight loss in obese humans

•Reviews evidence of biological mechanisms contributing to weight regain after diet.•Presents original hypothesis about action of these mechanisms.•Suggests mechanisms not part of regulatory system and enacted prior to weight loss.•Suggests mechanisms enacted irrespective of energy stores.•Suggests reframing as anti-weight loss vs. anti-starvation mechanisms.

Weight loss dieting remains the treatment of choice for the vast majority of obese individuals, despite the limited long-term success of behavioral weight loss interventions. The reasons for the near universal unsustainability of behavioral weight loss in [formerly] obese individuals have not been fully elucidated, relegating researchers to making educated guesses about how to improve obesity treatment, as opposed to developing interventions targeting the causes of weight regain. This article discusses research on several factors that may contribute to weight regain following weight loss achieved through behavioral interventions, including adipose cellularity, endocrine function, energy metabolism, neural responsivity, and addiction-like neural mechanisms. All of these mechanisms are engaged prior to weight loss, suggesting that these so called “anti-starvation” mechanisms are activated via reductions in energy intake, rather than depletion of energy stores. Evidence suggests that these mechanisms are not necessarily part of a homeostatic feedback system designed to regulate body weight, or even anti-starvation mechanisms per se. Although they may have evolved to prevent starvation, they appear to be more accurately described as anti-weight loss mechanisms, engaged with caloric restriction irrespective of the adequacy of energy stores. It is hypothesized that these factors may combine to create a biological disposition that fosters the maintenance of an elevated body weight and works to restore the highest sustained body weight, thus precluding the long-term success of behavioral weight loss. It may be necessary to develop interventions that attenuate these biological mechanisms in order to achieve long-term weight reduction in obese individuals.