Location, location, location: the CNS sites of leptin action dictate its regulation of homeostatic and hedonic pathways.
The increasing incidence of obesity and obesity-linked disease presents a serious global health threat. To develop truly effective therapies to modulate food intake and promote weight loss, we must understand the physiological regulators that underlie these processes. One crucial mediator of food intake and energy homeostasis is the adipose-derived hormone, leptin, which acts through neurons expressing the long form of the leptin receptor (LepRb). Although most investigation of leptin action has centered on the large population of LepRb neurons in the arcuate nucleus (ARC), this nucleus does not mediate all aspects of leptin action. Indeed, several hypothalamic and extrahypothalamic loci contain substantial numbers of LepRb neurons, each of which presumably mediates distinct aspects of leptin action, and the collective output of these various LepRb populations produces the totality of leptin function. This review will examine known central nervous system loci that contain LepRb neurons and the potential roles for discrete populations of LepRb neurons in the control of homeostatic and hedonic pathways by leptin. Understanding the unique neuroanatomical and functional roles for each locus of leptin action will be important to identify how specific aspects of food intake contribute to obesity.
Leinninger
G M
GM
Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0678, USA. ggehrke@med.umich.edu
D001069:Appetite Regulation / Q000502:physiology; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007031:Hypothalamus / Q000502:physiology*; D020738:Leptin / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology*; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D054411:Receptors, Leptin / Q000502:physiology*; D012201:Reward; D015398:Signal Transduction / Q000502:physiology
D020738:Leptin; D054411:Receptors, Leptin