Human biology of weight maintenance after weight loss.

One year after losing weight, most people have regained a significant part of the lost weight. As such, weight regain after weight loss has a negative impact on human health. The risk for weight regain is determined by psychosocial and behavioral factors as well as by various physiological and molecular parameters. Here, the latter intrinsic factors are reviewed and assembled into four functional modules, two related to the energy balance and two related to resistance against weight loss. Reported genetic factors do not reveal additional functional processes. The modules form nodes in a network describing the complex interactions of intrinsically determined weight maintenance. This network indicates that after an initial weight loss persons with a high baseline fat mass will most easily succeed in maintaining weight, because they can lose fat without raising stress in adipocytes and at the same time spare fat-free mass. However, continued weight loss and weight maintenance requires extra measures like increased physical activity, limited energy intake and a fat-free sparing composition of the diet. Eventually, this network may help to design novel therapeutic measures based on preventing the return effect of specific plasma factors or by preventing the accumulation of adipocyte cellular stress.