How the brain regulates food intake and body weight: the role of leptin.

The brain plays a key role in the regulation of energy homeostasis, balancing food intake and energy expenditure to maintain adipose tissue mass. A widely accepted model proposes that energy homeostasis is modulated by hormones that circulate in the blood in proportion to adipose tissue mass. A major candidate 'adiposity signal' to the brain is the adipocyte hormone, leptin; this inhibits neuropeptide circuits that promote anabolic metabolism, and stimulates those that promote catabolic metabolism. It is hypothesized that leptin-responsive circuits in the hypothalamus project to caudal brainstem neuronal groups that integrate satiety signals converging on the brain from the stomach and intestine following ingestion of food. Leptin signaling to the brainstem via hypothalamic pathways potentially increases the brain's motor and autonomic responses to satiety signals, leading to smaller individual meals, reduced cumulative food intake, and a lower body weight. This mechanism explains how leptin deficiency or defects in the brain's processing of leptin signaling can result in a sustained increase in food intake and obesity.