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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenal Glands / metabolism
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Amino Acid Sequence
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Animals
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Female
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Humans
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Hypothalamus / metabolism
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Male
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Melanocyte-Stimulating Hormones / antagonists & inhibitors
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Melanocyte-Stimulating Hormones / pharmacology
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Melanophores / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Obese
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Mice, Transgenic
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Molecular Sequence Data
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Obesity / etiology
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Organophosphorus Compounds / pharmacology
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Proteins / chemistry
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Proteins / genetics
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Proteins / pharmacology
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Proteins / physiology*
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RNA / genetics
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RNA / metabolism
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Receptor, Melanocortin, Type 3
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Receptor, Melanocortin, Type 4
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Receptors, Corticotropin / antagonists & inhibitors*
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Receptors, Corticotropin / metabolism
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Receptors, Peptide / antagonists & inhibitors*
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Receptors, Peptide / metabolism
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Recombinant Proteins / metabolism
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Signal Transduction
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Xenopus
Substances
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Organophosphorus Compounds
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Proteins
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Receptor, Melanocortin, Type 3
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Receptor, Melanocortin, Type 4
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Receptors, Corticotropin
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Receptors, Peptide
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Recombinant Proteins
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CGP 54626
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RNA
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Melanocyte-Stimulating Hormones