Is there evidence for a set point that regulates human body weight?

There is evidence for the idea that there is biological (active) control of body weight at a given set point. Body weight is the product of genetic effects (DNA), epigenetic effects (heritable traits that do not involve changes in DNA), and the environment. Regulation of body weight is asymmetric, being more effective in response to weight loss than to weight gain. However, regulation may be lost or camouflaged by Western diets, suggesting that the failure of biological control is due mainly to external factors. In this situation, the body’s ‘set point’ (i.e., a constant ‘body-inherent’ weight regulated by a proportional feedback control system) is replaced by various ‘settling points’ that are influenced by energy and macronutrient intake in order for the body to achieve a zero energy balance. In a world of abundance, a prudent lifestyle and thus cognitive control are preconditions of effective biological control and a stable body weight. This idea also impacts future genetic research on body weight regulation. Searching for the genetic background of excess weight gain in a world of abundance is misleading since the possible biological control is widely overshadowed by the effect of the environment. In regard to clinical practice, dietary approaches to both weight loss and weight gain have to be reconsidered. In underweight patients (e.g., patients with anorexia nervosa), weight gain is supported by biological mechanisms that may or may not be suppressed by hyperalimentation. To overcome weight loss-induced counter-regulation in the overweight, biological signals have to be taken into account. Computational modeling of weight changes based on metabolic flux and its regulation will provide future strategies for clinical nutrition.