Neuropeptide Y (NPY)

Endogenous Hormone

Neuropeptide Y (NPY) is a 36-amino-acid peptide and one of the most abundant and widely distributed neuropeptides in the mammalian brain. It is a member of the PP-fold family, which also includes peptide YY (PYY) and pancreatic polypeptide (PP), but unlike its gut-hormone relatives, NPY functions primarily as a central nervous system signaling molecule. Because it is a peptide the body produces itself, NPY is not sold or used as a drug — this page is an educational reference to its biology, which is central to understanding appetite, stress, and energy balance. NPY's most famous role is as a potent stimulant of appetite. It is produced in large amounts by NPY/AgRP neurons in the arcuate nucleus of the hypothalamus, the brain's principal hub for energy-balance control. When these neurons fire — for example during fasting or energy deficit — NPY release drives intense hunger and food-seeking behavior while promoting energy conservation. This makes NPY the functional opposite of the satiety signals: where PYY3-36 and GLP-1 suppress appetite, NPY powerfully promotes it, and the same neurons are directly inhibited by satiety hormones. This push-pull arrangement is a core feature of the gut–brain axis. NPY acts through a family of G-protein-coupled receptors (Y1 through Y5). Its appetite-stimulating effects are mediated mainly by the Y1 and Y5 receptors in the hypothalamus. Beyond feeding, NPY is a versatile regulator with effects that extend well past the appetite circuits: it is a potent vasoconstrictor and modulator of cardiovascular tone (often co-released with noradrenaline from sympathetic nerves), it shapes responses to stress and anxiety, and it contributes to circadian rhythm, memory, and seizure thresholds. This breadth is why NPY is studied across metabolism, psychiatry, and neurology. As the appetite-stimulating counterpart to the body's satiety peptides, NPY is closely tied to the other hormones discussed on this site. It belongs to the same structural family as peptide YY and pancreatic polypeptide, and its hypothalamic neurons are the very targets that ghrelin activates and that satiety signals like PYY, GLP-1-based drugs such as semaglutide, and the ancestral co-agonist oxyntomodulin work to suppress. For more on how these opposing signals interact, see our overviews of appetite regulation, satiety hormones, and the gut–brain axis.