Leptin activates hypothalamic CART neurons projecting to the spinal cord

The adipocyte-derived hormone leptin decreases body weight in part by activ ating the sympathetic nervous system, resulting in increased thermogenesis and energy expenditure. We investigated hypothalamic pathways underlying le ptin's effects on stimulating the sympathetic nervous system. We found that leptin activates neurons in the retrochiasmatic area (RCA) and lateral arc uate nucleus (Arc) that innervate the thoracic spinal cord and also contain cocaine- and amphetamine-regulated transcript (CART). We also found that m ost CART-containing neurons in the RCA and Are of the hypothalamus also con tain proopiomelanocortin (POMC) mRNA. The finding that leptin activates CAR T/POMC neurons innervating sympathetic preganglionic neurons in the thoraci c spinal cord suggests that this pathway may contribute to the increased th ermogenesis and energy expenditure and decreased body weight observed follo wing leptin administration.