Agouti-related protein also called Agouti-related peptide (AgRP) is a neuropeptide produced in the brain (in the arcuate nucleus of the hypothalamus) by the AgRP/NPY neuron that increases appetite and decreases metabolism and energy expenditure. It is one of the most potent and long-lasting of appetite stimulators. Understanding the role AgRP plays in weight gain may assist in developing pharmaceutical models for treating obesity. It was identified independently by two teams based on sequence similarity with agouti, a protein synthetized in the skin that control coat color. [1][4]

The appetite stimulating effects of AgRP are inhibitied by the hormone leptin. Adipocytes secrete leptin in response to food intake. This hormone acts in the arcuate nucleus and inhibits the AgRP/NPY neuron from releasing orexigenic peptides. [3]

AGRP has been demonstrated to be an inverse agonist of melanocortin receptors, specifically, MC3-R and MC4-R. This inverse agonism not only antagonizes the action of melanocortin agonists, such as alpha-MSH but also further decreases the cAMP produced by the affected cells. AgRP levels have been found to be elevated in obese males. [4]

References:

[1]. Shutter, J. R.; Graham, M.; Kinsey, A. C.; Scully, S.; Luthy, R. and Stark K. L. Hypothalamic expression of ART, a novel gene related to agouti, is up- regulated in obese and diabetic mutant mice. Genes Dev 11 (5):593-602, 1997.

[2]. Ollmann, M. M.; Wilson, B. D.; Yang, Y.-K.; Kerns, J. A.; Chen, Y.; Gantz, I.; Barsh, G. S. : Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278: 135-138, 1997.

[3]. Enriori PJ, Evans AE, Sinnayah P, Jobst EE, Tonelli-Lemos L, Billes SK, Glavas MM, Grayson BE, Perello M, Nillni EA, Grove KL, Cowley MA. Cell Metab. 2007 Mar 7;5(3):181-194.

[4]. Katsuki, A.; Sumida, Y.; Gabazza, E. C.; Murashima, S.; Tanaka, T.; Furuta, M.; Araki-Sasaki, R.; Hori, Y.; Nakatani, K.; Yano, Y.; Adachi, Y. : Plasma levels of agouti-related protein are increased in obese men. J. Clin. Endocr. Metab. 86: 1921-1924, 2001.