PMID:9311920

Citation	Ollmann, MM, Wilson, BD, Yang, YK, Kerns, JA, Chen, Y, Gantz, I and Barsh, GS (1997) Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278:135-8
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.
Links	PubMed
Keywords	Adrenal Glands/metabolism; Amino Acid Sequence; Animals; Female; Humans; Hypothalamus/metabolism; Male; Melanocyte-Stimulating Hormones/antagonists & inhibitors; Melanocyte-Stimulating Hormones/pharmacology; Melanophores/metabolism; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Obese; Mice, Transgenic; Molecular Sequence Data; Obesity/etiology; Organophosphorus Compounds/pharmacology; Proteins/chemistry; Proteins/genetics; Proteins/pharmacology; Proteins/physiology; RNA/genetics; RNA/metabolism; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Receptors, Corticotropin/antagonists & inhibitors; Receptors, Corticotropin/metabolism; Receptors, Peptide/antagonists & inhibitors; Receptors, Peptide/metabolism; Recombinant Proteins/metabolism; Signal Transduction; Xenopus
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