Clinical endocrinology and metabolism. Regulation of energy homeostasis by peripheral signals.

The increased incidence of obesity makes it imperative to understand the regulation of food intake and body weight. We review the signals that interact with the brain to control energy homeostasis, i.e. energy intake and expenditure. Three broad categories can be distinguished. Signals generated in the gastrointestinal tract during meals ('satiety' signals, e.g. cholecystokinin) elicit satiation and contribute to stopping the meal. The potency of these acutely acting signals must be increased if they are to be used therapeutically. Hormonal signals whose secretion is proportional to body fat (adiposity signals, leptin and insulin) robustly reduce food intake and body weight by directly stimulating receptors locally in the brain. Therapeutic applications will have to find ways to circumvent the systemic actions of these hormones, targeting only the brain. Satiety and adiposity signals interact with neuronal circuits in the brain that utilize myriad neurotransmitters to cause net catabolic or anabolic responses. Considerable effort is being directed towards finding ways to intervene in specific circuits to help accomplish weight loss.