NPYAgRPneuronen

NPY/AgRP neurons, often referred to as NPY–AgRP neurons, are a population located in the arcuate nucleus of the hypothalamus. They coexpress neuropeptide Y (NPY) and agouti-related peptide (AgRP) and are predominantly GABAergic. These neurons are key regulators of energy balance and feeding behavior, becoming more active during energy deficit and more inhibited by satiety signals. Ghrelin, a stomach-derived hormone that stimulates appetite, strongly activates these neurons, while leptin and insulin—signals of adiposity and nutrient status—tend to suppress them. Activation of NPY/AgRP neurons promotes food intake and reduces energy expenditure, contributing to hunger and the return to energy balance after fasting.

A central mechanism involves interaction with the melanocortin system. AgRP acts as an endogenous antagonist (and possibly inverse agonist) of melanocortin receptors, particularly MC4R, opposing the anorexigenic effects of melanocortin peptides such as alpha-MSH. NPY released from these neurons can also influence feeding through its own receptor subtypes. The neurons project widely within the hypothalamus and connected brain regions, including the paraventricular nucleus (PVN), dorsomedial hypothalamus, and lateral hypothalamic area, thereby modulating neuroendocrine and autonomic outputs that regulate hunger, glucose homeostasis, and energy expenditure.

Clinical and research relevance centers on the role of NPY/AgRP signaling in body weight regulation and metabolic control. Disruptions or alterations of this pathway influence susceptibility to obesity and other energy balance disorders, and the network remains a focus for potential appetite-control therapies.