Leptin, a hormone secreted by adipocytes, acts on the hypothalamus to regulate appetite and neuroendocrine function. In the hypothalamus, both the arcuate nucleus and the ventromedial nucleus express leptin receptors. Specific neurons in the arcuate nucleus regulate appetite and reproduction. In contrast, neurons in the ventromedial nucleus regulate bone mass. The melanocortin system is the downstream pathway for regulating appetite and neuroendocrine function. In contrast, the sympathetic nervous system is the downstream pathway for regulating bone mass. Leptin, in regulating food intake and body weight, acts, in part, by inhibiting the synthesis of neuropeptide Y and its release from the hypothalamus. The leptin and insulin pathways may interact and may be important in the pathogenesis of the metabolic syndrome. © 2006 Wiley-Liss, Inc.