Leptin Receptor Signaling and Action in the Central Nervous System

LESHAN, REBECCA L., MARIE BJORNHOLM, HEIKE MUNZBERG, AND MARTIN G. MYERS JR. Leptin receptor signaling and action in the central nervous system. Obesity. 2006;14(Suppl 5):208S-212S. The increasing incidence of obesity in developed nations represents an ever-growing challenge to health care by promoting diabetes and other diseases. The discovery of the hormone, leptin, a decade ago has facilitated the acquisition of new knowledge regarding the regulation of energy bal- ance. A great deal remains to be discovered regarding the molecular and anatomic actions of leptin, however. Here, we discuss the mechanisms by which leptin activates intra- cellular signals, the roles that these signals play in leptin action in vivo, and sites of leptin action in vivo. Using "reporter" mice, in which LRb-expressing (long form of the leptin receptor) neurons express the histological marker, -galactosidase, coupled with the detection of LRb-medi- ated signal transducer and activator of transcription 3 sig- naling events, we identified LRb expression in neuronal populations both within and outside the hypothalamus. Un- derstanding the regulation and physiological function of these myriad sites of central leptin action will be a crucial next step in the quest to understand mechanisms of leptin action and energy balance.