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Gene Review

Agrp  -  agouti related neuropeptide

Mus musculus

Synonyms: Agouti-related protein, Agrt, Art, agouti related protein
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Disease relevance of Agrp


Psychiatry related information on Agrp


High impact information on Agrp


Chemical compound and disease context of Agrp


Biological context of Agrp


Anatomical context of Agrp


Associations of Agrp with chemical compounds

  • Hypothalamic mRNA levels of agouti- related protein (AGRP), an orexigenic melanocortin receptor antagonist, increased after GHRP-2 treatment [20].
  • In addition, the present results confirmed the downregulating effects of leptin on the expression of AGRP mRNA in the hypothalamic arcuate nucleus (ARC), and demonstrated that this effect was more apparent in ADX mice treated with corticosterone than in ADX mice not supplemented with corticosterone [21].
  • In muscle, however, 2 weeks of high fat feeding did not result in changes in insulin sensitivity or in triglyceride content. mRNA expression levels of NPY, AgRP, POMC, and CART in the hypothalamus were not different between the groups [22].
  • The persistent effect seems to be due to inhibition of the fasting-induced up-regulation of expression of hypothalamic orexigenic neuropeptides neuropeptide Y and agouti-related protein and down-regulation of expression of anorexigenic neuropeptides pro-opiomelanocortinalpha-melanocyte-stimulating hormone and cocaine-amphetamine-related transcript [23].
  • ASIP adopts the inhibitor cystine knot fold and, along with AgRP, are the only known mammalian proteins in this structure class [24].

Physical interactions of Agrp


Regulatory relationships of Agrp

  • These studies demonstrate that hypothalamic AgRP mRNA and immunoreactivity are upregulated with fasting and that these increases are not affected by NPY deficiency [26].
  • Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting [2].

Other interactions of Agrp


Analytical, diagnostic and therapeutic context of Agrp

  • To investigate the potential role of the amino-terminal residues, we compared the function of full-length and carboxyl-terminal fragments of Agrp and Agouti protein in a sensitive bioassay based on pigment dispersion in Xenopus melanophores [30].
  • Using a sensitive solution hybridization/S1 nuclease protection assay, we found no significant difference in Agrp messenger RNA (mRNA) levels (pg/microg total RNA +/- SEM) in obese rats (n = 5), compared with lean controls (n = 5): 0.46 +/- 0.06 vs. 0.47 +/- 0.06 (P = 0.9) [31].
  • Similarly, no difference in Agrp expression was found using in situ hybridization or semiquantitative RT-PCR [31].
  • Sequence analysis of this gene, named ART, for agouti-related transcript, predicts a 132-amino-acid protein that is 25% identical to human agouti [32].
  • All of these residues are conserved in the agouti-related transcript, ART, whose expression is up-regulated in animal models of obesity [33].


  1. The role of agouti-related protein in regulating body weight. Wilson, B.D., Ollmann, M.M., Barsh, G.S. Molecular medicine today. (1999) [Pubmed]
  2. Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting. Mizuno, T.M., Mobbs, C.V. Endocrinology (1999) [Pubmed]
  3. Role of leptin and melanocortin signaling in uremia-associated cachexia. Cheung, W., Yu, P.X., Little, B.M., Cone, R.D., Marks, D.L., Mak, R.H. J. Clin. Invest. (2005) [Pubmed]
  4. Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. Gao, Q., Wolfgang, M.J., Neschen, S., Morino, K., Horvath, T.L., Shulman, G.I., Fu, X.Y. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  5. Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Qian, S., Chen, H., Weingarth, D., Trumbauer, M.E., Novi, D.E., Guan, X., Yu, H., Shen, Z., Feng, Y., Frazier, E., Chen, A., Camacho, R.E., Shearman, L.P., Gopal-Truter, S., MacNeil, D.J., Van der Ploeg, L.H., Marsh, D.J. Mol. Cell. Biol. (2002) [Pubmed]
  6. Leptin regulation of Agrp and Npy mRNA in the rat hypothalamus. Korner, J., Savontaus, E., Chua, S.C., Leibel, R.L., Wardlaw, S.L. J. Neuroendocrinol. (2001) [Pubmed]
  7. Agouti-related protein functions as an inverse agonist at a constitutively active brain melanocortin-4 receptor. Haskell-Luevano, C., Monck, E.K. Regul. Pept. (2001) [Pubmed]
  8. Drug target discovery by pharmacogenetics: mutations in the melanocortin system and eating disorders. Adan, R.A., Vink, T. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. (2001) [Pubmed]
  9. A biochemical function for attractin in agouti-induced pigmentation and obesity. He, L., Gunn, T.M., Bouley, D.M., Lu, X.Y., Watson, S.J., Schlossman, S.F., Duke-Cohan, J.S., Barsh, G.S. Nat. Genet. (2001) [Pubmed]
  10. Overexpression of Agrt leads to obesity in transgenic mice. Graham, M., Shutter, J.R., Sarmiento, U., Sarosi, I., Stark, K.L. Nat. Genet. (1997) [Pubmed]
  11. Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. Yamada, M., Miyakawa, T., Duttaroy, A., Yamanaka, A., Moriguchi, T., Makita, R., Ogawa, M., Chou, C.J., Xia, B., Crawley, J.N., Felder, C.C., Deng, C.X., Wess, J. Nature (2001) [Pubmed]
  12. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Ollmann, M.M., Wilson, B.D., Yang, Y.K., Kerns, J.A., Chen, Y., Gantz, I., Barsh, G.S. Science (1997) [Pubmed]
  13. PI3K integrates the action of insulin and leptin on hypothalamic neurons. Xu, A.W., Kaelin, C.B., Takeda, K., Akira, S., Schwartz, M.W., Barsh, G.S. J. Clin. Invest. (2005) [Pubmed]
  14. Nicotine withdrawal increases body weight, neuropeptide Y and Agouti-related protein expression in the hypothalamus and decreases uncoupling protein-3 expression in the brown adipose tissue in high-fat fed mice. Fornari, A., Pedrazzi, P., Lippi, G., Picciotto, M.R., Zoli, M., Zini, I. Neurosci. Lett. (2007) [Pubmed]
  15. Effect of Agouti-related protein in regulation of the hypothalamic-pituitary-thyroid axis in the melanocortin 4 receptor knockout mouse. Fekete, C., Marks, D.L., Sarkar, S., Emerson, C.H., Rand, W.M., Cone, R.D., Lechan, R.M. Endocrinology (2004) [Pubmed]
  16. Structure activity studies of the melanocortin-4 receptor by in vitro mutagenesis: identification of agouti-related protein (AGRP), melanocortin agonist and synthetic peptide antagonist interaction determinants. Haskell-Luevano, C., Cone, R.D., Monck, E.K., Wan, Y.P. Biochemistry (2001) [Pubmed]
  17. Anorexigenic melanocortin signaling in the hypothalamus is augmented in association with failure-to-thrive in a transgenic mouse model for Prader-Willi syndrome. Ge, Y., Ohta, T., Driscoll, D.J., Nicholls, R.D., Kalra, S.P. Brain Res. (2002) [Pubmed]
  18. Age-dependent hypothalamic expression of neuropeptides in wild-type and melanocortin-4 receptor-deficient mice. Arens, J., Moar, K.M., Eiden, S., Weide, K., Schmidt, I., Mercer, J.G., Simon, E., Korf, H.W. Physiol. Genomics (2003) [Pubmed]
  19. Peripherally administered [Nle4,D-Phe7]-alpha-melanocyte stimulating hormone increases resting metabolic rate, while peripheral agouti-related protein has no effect, in wild type C57BL/6 and ob/ob mice. Hoggard, N., Rayner, D.V., Johnston, S.L., Speakman, J.R. J. Mol. Endocrinol. (2004) [Pubmed]
  20. GH-releasing peptide-2 increases fat mass in mice lacking NPY: indication for a crucial mediating role of hypothalamic agouti-related protein. Tschöp, M., Statnick, M.A., Suter, T.M., Heiman, M.L. Endocrinology (2002) [Pubmed]
  21. Effects of leptin and corticosterone on the expression of corticotropin-releasing hormone, agouti-related protein, and proopiomelanocortin in the brain of ob/ob mouse. Arvaniti, K., Huang, Q., Richard, D. Neuroendocrinology (2001) [Pubmed]
  22. High fat diet induced hepatic insulin resistance is not related to changes in hypothalamic mRNA expression of NPY, AgRP, POMC and CART in mice. Heijboer, A.C., Voshol, P.J., Donga, E., van Eden, C.G., Havekes, L.M., Romijn, J.A., Pijl, H., Corssmit, E.P. Peptides (2005) [Pubmed]
  23. Effect of the anorectic fatty acid synthase inhibitor C75 on neuronal activity in the hypothalamus and brainstem. Gao, S., Lane, M.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  24. Structures of the agouti signaling protein. McNulty, J.C., Jackson, P.J., Thompson, D.A., Chai, B., Gantz, I., Barsh, G.S., Dawson, P.E., Millhauser, G.L. J. Mol. Biol. (2005) [Pubmed]
  25. Syndecan-3 modulates food intake by interacting with the melanocortin/AgRP pathway. Reizes, O., Benoit, S.C., Strader, A.D., Clegg, D.J., Akunuru, S., Seeley, R.J. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  26. Effects of neuropeptide Y deficiency on hypothalamic agouti-related protein expression and responsiveness to melanocortin analogues. Marsh, D.J., Miura, G.I., Yagaloff, K.A., Schwartz, M.W., Barsh, G.S., Palmiter, R.D. Brain Res. (1999) [Pubmed]
  27. Novel agouti-related-protein-based melanocortin-1 receptor antagonist. Thirumoorthy, R., Holder, J.R., Bauzo, R.M., Richards, N.G., Edison, A.S., Haskell-Luevano, C. J. Med. Chem. (2001) [Pubmed]
  28. Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Marsh, D.J., Hollopeter, G., Huszar, D., Laufer, R., Yagaloff, K.A., Fisher, S.L., Burn, P., Palmiter, R.D. Nat. Genet. (1999) [Pubmed]
  29. Elongation studies of the human agouti-related protein (AGRP) core decapeptide (Yc[CRFFNAFC]Y) results in antagonism at the mouse melanocortin-3 receptor. Joseph, C.G., Bauzo, R.M., Xiang, Z., Shaw, A.M., Millard, W.J., Haskell-Luevano, C. Peptides (2003) [Pubmed]
  30. Down-regulation of melanocortin receptor signaling mediated by the amino terminus of Agouti protein in Xenopus melanophores. Ollmann, M.M., Barsh, G.S. J. Biol. Chem. (1999) [Pubmed]
  31. Effects of leptin receptor mutation on Agrp gene expression in fed and fasted lean and obese (LA/N-faf) rats. Korner, J., Wardlaw, S.L., Liu, S.M., Conwell, I.M., Leibel, R.L., Chua, S.C. Endocrinology (2000) [Pubmed]
  32. Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Shutter, J.R., Graham, M., Kinsey, A.C., Scully, S., Lüthy, R., Stark, K.L. Genes Dev. (1997) [Pubmed]
  33. Melanocortin receptor binding determinants in the agouti protein. Kiefer, L.L., Veal, J.M., Mountjoy, K.G., Wilkison, W.O. Biochemistry (1998) [Pubmed]
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