AGRP

Agouti-related peptide (AgRP) is a neuropeptide produced primarily by neurons in the arcuate nucleus of the hypothalamus. It is encoded by the AGRP gene and is part of the agouti signaling protein family. AgRP is expressed in a population of neurons that also produce neuropeptide Y (NPY) and agouti-related peptide–producing cells project widely within the brain to regulate feeding and energy balance.

AgRP acts as an endogenous antagonist of melanocortin receptors, particularly MC4R, and also functions as an inverse agonist at MC4R. By inhibiting melanocortin signaling, AgRP promotes food intake and can decrease energy expenditure. In the arcuate nucleus, AgRP neurons are co-expressed with NPY and become more active during periods of energy deficit; they contribute to the orexigenic drive that increases appetite. Central administration of AgRP increases feeding in animal models, and sustained changes in AgRP levels can influence body weight.

Regulation of AgRP is tightly linked to energy status. Fasting or negative energy balance increases AgRP mRNA and peptide levels, while signals associated with energy sufficiency—such as leptin and insulin—suppress AgRP expression. Ghrelin, another hunger hormone from the stomach, stimulates AgRP/NPY neurons to amplify hunger signals.

Physiologically, AgRP neurons are key components of a broader network controlling appetite and glucose homeostasis. Dysregulation of the AgRP–melanocortin pathway has been implicated in obesity and related metabolic disorders in animal studies, and it remains a focus of interest for therapies aimed at modulating melanocortin signaling to influence feeding behavior.