REGULATION OF HYPOTHALAMIC PROOPIOMELANOCORTIN MESSENGER-RNA BY LEPTIN IN OB OB MICE/

The hormone leptin acts on the brain to regulate feeding, metabolism, and reproduction; however, its cellular targets and molecular mechanis ms of action remain to be fully elucidated. The melanocortins, which a re derived from the precursor proopiomelanocortin (POMC), are also imp licated in the physiological regulation of body weight. POMC-containin g neurons express the leptin receptor, and thus it is conceivable that the POMC gene itself may be part of the signaling pathway involved in leptin's action on the brain. Using in situ hybridization and compute rized image analysis, we tested the hypothesis that the POMC gene is a target for regulation by leptin by comparing cellular levels of POMC mRNA in the hypothalamus among groups of leptin-deficient (ob/ob) mice , leptin-treated ob/ob mice, and wild-type controls. POMC mRNA levels were significantly reduced throughout the arcuate nucleus in vehicle-t reated ob/ob mice relative to wild-type controls, whereas POMC mRNA le vels in leptin-treated ob/ob mice were indistinguishable from wild typ e controls. These observations suggest that one or more products of PO MC serve as an integrative link between leptin and the central mechani sms governing body weight regulation and reproduction.