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Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan
¹ Department of Regulation Biology, Saitama University, Saitama 378-8570, Japan

(Requests for offprints should be addressed to M Mori; Email: mmori{at}med.gunma-u.ac.jp)

The brain hypothalamus coordinates extra-hypothalamic regions to maintain energy homeostasis through the regulation of food intake and energy expenditure. A number of anorexigenic and orexigenic molecules in the hypothalamic nuclei participate in the control of energy homeostasis. Leptin and pro-opiomelanocortin (POMC)-derived -melanocyte-stimulating hormone are key anorectic molecules, and the leptin receptor and POMC gene are both expressed in the hypothalamic arcuate nucleus. Although it has been considered that melanocortin signaling is localized downstream to leptin signaling, data have accumulated to support the concept of a leptin-independent melanocortin signaling system. We focus on and review the melanocortin signaling system that functions dependently or independently of leptin signaling in the regulation of energy homeostasis.