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. 1997 Oct 3;278(5335):135-8.
doi: 10.1126/science.278.5335.135.

Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein

M M Ollmann  1 , B D Wilson, Y K Yang, J A Kerns, Y Chen, I Gantz, G S Barsh
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Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein

M M Ollmann et al. Science. .

Erratum in

  • Science 1998 Sep 11;281(5383):1615

Abstract

Expression of Agouti protein is normally limited to the skin where it affects pigmentation, but ubiquitous expression causes obesity. An expressed sequence tag was identified that encodes Agouti-related protein, whose RNA is normally expressed in the hypothalamus and whose levels were increased eightfold in ob/ob mice. Recombinant Agouti-related protein was a potent, selective antagonist of Mc3r and Mc4r, melanocortin receptor subtypes implicated in weight regulation. Ubiquitous expression of human AGRP complementary DNA in transgenic mice caused obesity without altering pigmentation. Thus, Agouti-related protein is a neuropeptide implicated in the normal control of body weight downstream of leptin signaling.

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