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Increased adiposity leads to increased leptin
production in fat tissue. Leptin stimulates neurons in the arcuate nucleus
of the hypothalamus that coexpress the anorexigenic hormones a
melanocyte-stimulating hormone (a-MSH,
a cleavage product of proopiomelanocortin [POMC]) and cocaine- and
amphetamine-regulated transcript. Leptin also inhibits neurons in the
arcuate nucleus that coexpress the orexigenic hormones agouti-related
protein and neuropeptide Y. The neurons in the arcuate nucleus project to
other regions of the hypothalamus (including the paraventricular nucleus
and the lateral hypothalamic area–parafornical area), where
a-MSH
binds to its receptor, MC4R, resulting in an up-regulation of anorexigenic
effectors such as corticotropin-releasing hormone (CRH) and
thyrotropin-releasing hormone (TRH) and a down-regulation of orexigenic
effectors such as melanin-concentrating hormone (MCH) and orexin.
Agouti-related protein acts as an antagonist of MC4R.
Reprint with permission from List JF, Habener
JF. New Eng J Med 2003;348:1160-1163.
Copyright ©2003 Massachusetts Medical Society.
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