Agouti related peptide

Agouti-related peptide/Agouti-related protein (AgRP) is a neuropeptide produced by a subpopulation of neurones in the ventromedial part of the arcuate nucleus in the mammalian hypothalamus. The same neurons also produce neuropeptide Y (NPY). AgRP and NPY are both potent simulators of appetite when injected centrally (i.e. directly into the brain), and they decrease metabolism and energy expenditure.

AgRP acts as an inverse agonist at melanocortin 4 (MC4) receptors in the brain, thus it opposes the actions of the satiety-inducing neuropeptide alpha-melanocyte stimulating hormone, which is produced by neurones mainly in the dorsomedial part of the acrcuate nucleus. One of the major sites at which AgRP acts is in the paraventricular nucleus, which is directly innervated by the NPY/AgRP neurons, and where MC4 receptors are expressed on several neuronal populations, including on magnocellular oxytocin neurones and on presympathetic neurones. The NPY/AgRP neurones are directly activated in response to ghrelin, a hormone released from the empty stomach that is a potent stimulator of hunger. Conversely, they are inhibited by leptin, a hormone secreted by adipocytes in proportion to total body fat mass.

The NPY/AgRP neurones use GABA as a conventional neurotransmitter. Transgenic mice engineered to be deficient from birth in either NPY or AgRP or both maintain a relatively normal body weight. However,if these neurones are selectively lesioned in adult mice, then the mice stop eating.