NPYAgRP

NPY/AgRP neurons are a population of neurons in the arcuate nucleus of the hypothalamus that coexpress neuropeptide Y (NPY) and agouti-related peptide (AgRP). These neurons are GABAergic and project broadly to hypothalamic and brainstem regions, where they coordinate feeding and energy expenditure. The coexpression of NPY and AgRP allows a rapid, complementary control of appetite: NPY acts on Y1 and Y5 receptors to stimulate food intake, while AgRP functions as a competitive antagonist and inverse agonist at melanocortin receptors MC3R and MC4R, reducing melanocortin signaling that normally suppresses appetite.

NPY/AgRP neurons also release GABA, contributing to fast inhibitory signaling to downstream targets such as POMC/CART neurons in the arcuate nucleus and other feeding centers. The net effect is a strong promotion of feeding during energy deficit.

Metabolic state regulates these neurons: ghrelin, a meal-initiating hormone, activates NPY/AgRP neurons and increases hunger, whereas leptin and insulin suppress their activity in proportion to energy stores. Fasting increases their firing and peptide release; refeeding and satiety signals reduce activity.

Anatomically, NPY/AgRP neurons project from the arcuate nucleus to the paraventricular nucleus, lateral hypothalamus, dorsomedial nucleus, and brainstem nuclei, integrating hormonal, sensory, and circadian information to control food intake and energy balance.

Disruption of the melanocortin system or dysregulation of NPY/AgRP signaling has been linked to obesity and metabolic disease in preclinical models, making these neurons and their receptors targets of interest for therapeutic strategies. Research continues to unravel how temporal patterns of peptide release shape feeding behavior and energy homeostasis.