Here we summarize recent progress in the biology of leptin, concentrat
ing on its central nervous system (CNS) actions. The product of the ob
gene, leptin is a circulating hormone produced by white adipose tissu
e that has potent effects on feeding behavior, thermogenesis and neuro
endocrine responses. Leptin regulates energy homeostasis, as its absen
ce in rodents and humans causes severe obesity. We consider the physio
logical mechanisms underlying leptin action, along with several novel
hypothalamic neuropeptides that affect food intake and body weight. Th
e molecular causes of several other obesity syndromes are discussed to
illuminate how the CNS regulates body weight. We describe neural circ
uits that are downstream of leptin receptors and propose a model linki
ng populations of leptin-responsive neurons with effector neurons unde
rlying leptin's endocrine, autonomic and behavioral effects.