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Neuropeptide Y (NPY) is a 36 amino acid peptide neurotransmitter found in the brain and autonomic nervous system. It augments the vasoconstrictor effects of noradrenergic neurons.

NPY has been associated with a number of physiologic processes in the brain, including the regulation of energy balance, memory and learning, and epilepsy (1).

Role in regulation of feeding

NPY's role in regulating energy balance is well known. It forms part of the "lipostat" system along with leptin and corticotropin-releasing hormone (CRH). High NPY levels in the cerebrospinal fluid are associated with high food intake and decreased physical activity. Leptin, produced by adipocytes in response to high fat levels is detected by the arcuate nucleus in the hypothalamus. Increased arcuate nucleus activity acts on the paraventricular nucleus to inhibit the production of NPY at that site, thus reducing feeding behaviour. Arcuate nucleus activity also stimulates the release of CRH which further decreases feeding and increases energy expenditure.


The receptor protein that NPY operates on is a G-protein coupled receptor in the rhodopsin like GPCR family. These receptors are metabotropic, causing metabolic changes in the target cell rather than directly opening ion channels. The protein contains seven membrane spanning domains and six subtypes have been identified at this time. Subtypes Y1 and Y5 have known roles in the regulation of feeding. This receptor family is one of the most highly conserved between species yet found.


  • Official Symbol: NPY
  • Gene type: protein coding
  • Gene name: NPY
  • Gene description: neuropeptide Y
  • Organism: Homo sapiens
  • Gene aliases: PYY4
  • Chromosome: 7; Location: 7p15.1

Literature review

Leu7Pro polymorphism of the NPY gene associates with alterations in FFA metabolism but does not have an impact on insulin sensitivity, insulin secretion, or glucose metabolism. (2)

Genetically determined changes in NPY levels lead to widespread consequences in the control of sympathoadrenal, metabolic, and hormonal balance in healthy subjects.(3)

The Leu7Pro polymorphism of preproNPY is related to decreased level of basal sympathetic activity, decreased insulin secretion, and delayed ghrelin suppression during oral glucose tolerance test. (4)

NPY is a mediator and a marker of chronic stress in humans, including extreme trauma and posttraumatic stress disorder. (5)

Aging women have increased NPY gene expression. Functional relationship between NPY and POMC neurons demonstrated in other species also exists in human. Increase in NPY mRNA in older women may be due to factors other than ovarian failure of menopause.(6)