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The Journal of Neuroscience, October 15, 2002, 22(20):9048-9052
The Catabolic Action of Insulin in the Brain Is Mediated by
Melanocortins
Stephen C.
Benoit1,
Ellen L.
Air1,
Lique M.
Coolen2,
Richelle
Strauss1,
Alana
Jackman3,
Deborah J.
Clegg1,
Randy J.
Seeley1, and
Stephen C.
Woods1
Departments of 1 Psychiatry and 2 Cell
Biology, Neurobiology, and Anatomy, University of Cincinnati,
Cincinnati, Ohio 45267, and 3 Procter & Gamble
Pharmaceuticals, Mason, Ohio 45040
Like leptin, the pancreatic hormone insulin is an important
adiposity signal to the brain. We report that the hypothalamic melanocortin system is an important target of the actions of
insulin to regulate food intake and body weight. Hypothalamic
neurons expressing insulin receptors were found to coexpress the
melanocortin precursor molecule pro-opiomelanocortin (POMC), and
administration of insulin into the third cerebral ventricle of fasted
rats increased expression of POMC mRNA. Finally, a subthreshold dose of
the melanocortin antagonist SHU-9119 prevented the reduction in food
intake caused by third-ventricular insulin administration. These data
suggest that the hypothalamic melanocortin system mediates the anorexic effects of central insulin, as well as of leptin.
Key words:
insulin; melanocortins; POMC; food intake; obesity; leptin
Copyright © 2002 Society for Neuroscience 0270-6474/02/22209048-05$05.00/0
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