Neuropeptide Y

Overview
Neuropeptide Y (NPY) is a 36 amino acid peptide neurotransmitter found in the brain and autonomic nervous system.

NPY has been associated with a number of physiologic processes in the brain, including the regulation of energy balance, memory and learning, and epilepsy. The main effect is increased food intake and decreased physical activity.

NPY is secreted by the hypothalamus, and in addition to increasing food intake, it increases the proportion of energy stored as fat and blocks nociceptive signals to the brain.

NPY also augments the vasoconstrictor effects of noradrenergic neurons.

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.

Correlation with stress and diet
Studies of mice and monkeys show that repeated stress— and a high-fat, high-sugar diet— stimulate the release of neuropeptide Y, causing fat to build up in the abdomen. Researchers believe that by manipulating levels of the appetite hormone, they could make fat melt from areas where it was not desired and accumulate at sites where it is needed.

Higher levels of NPY may be associated with resilience against and recovery from posttraumatic stress disorder.

Receptors
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 five subtypes have been identified in mammals, four of which are functional in humans. Subtypes Y1 and Y5 have known roles in the stimulation of feeding while Y2 and Y4 seem to have roles in appetite inhibition (satiety). Some of these receptors are among the most highly conserved neuropeptide receptors.