Physiology of Energy Intake in the Weight-Reduced State.

Physiological adaptations to intentional weight loss can facilitate weight regain. This review summarizes emerging findings on hypothalamic and brainstem circuitry in the regulation of body weight and identifies promising areas for research to improve therapeutic interventions for sustainable weight loss. There is good evidence that body weight is actively regulated in a homeostatic fashion similar to other physiological parameters. However, the defended level of body weight is not fixed but rather depends on environmental conditions and genetic background in an allostatic fashion. In an environment with plenty of easily available energy-dense food and low levels of physical activity, prone individuals develop obesity. In a majority of individuals with obesity, body weight is strongly defended through counterregulatory mechanisms, such as hunger and hypometabolism, making weight loss challenging. Among the options for treatment or prevention of obesity, those directly changing the defended body weight would appear to be the most effective ones. There is strong evidence that the mediobasal hypothalamus is a master sensor of the metabolic state and an integrator of effector actions responsible for the defense of adequate body weight. However, other brain areas, such as the brainstem and limbic system, are also increasingly implicated in body weight defense mechanisms and may thus be additional targets for successful therapies.