In physiology, neuropeptide Y (NPY) is a peptide chemical messenger secreted by the hypothalamus, that portion of the brain that controls hunger, thirst, fatigue, and body temperature. NPY plays a role in various basic processes in the brain, including energy regulation, memory formation, and seizure activity. The main effect of NPY is to promote increased food intake and decreased physical activity in response to a plummeting blood sugar level. In addition to increasing food intake, it increases the percentage of calories stored as fat and blocks pain receptor signals to the brain. NPY also increases constriction of blood vessels.
Injection of antibodies that counteract neuropeptide Y blocks the urge to eat in rodents. Leptin, a naturally occurring appetite suppressant, inhibits NPY formation and release. Disruption of the gene's coding for neuropeptide Y in genetically obese mice leads to weight loss or normal weight maintenance. When the NPY-deficient mice reproduce with regular obese mice, the progeny also experience less obesity. These studies implicate NPY in the drive to eat and in overeating leading to obesity.
Investigators have discovered that the hypothalamus secretes neuropeptide Y during emotional stress. In addition to stimulating a stressed individual to eat, the peptide also dampens the "fight or flight" response, defusing emotional stress. Variations in the genetic code for neuropeptide Y expression produce variations in resilience to emotional trauma and stress. Many drug companies are trying to produce drugs that bind to NPY receptors to achieve an anxiety-reducing effect.
Although the neuropeptide has a calming effect, it also interferes with immune defenses by binding to a receptor called “Y1.” Y1 receptor signaling inhibits responses by the body’s first-line immune cells. Secondly, Y1 receptor signaling suppresses activation of the second wave of adaptive immune lymphocytes. This finding emphasizes the association of suppression of the immune response and higher susceptibility to infection with NPY. Possibly, the link between times of increased stress and increased susceptibility to infection is due to increased NPY during these times.
Other studies have identified a genetic linkage between increased NPY and coronary artery disease (CAD). On the other hand, the application of NPY antibodies to atherosclerotic arteries reduces the affected atherosclerotic areas by 50 percent. Two variants of NPY are associated with atherosclerosis. The artery-constricting and plaque-inducing effects of neuropeptide Y may partially explain the common link between obesity and coronary artery disease.
Neuropeptide Y also plays a critical part in pain perception at various locations within the central nervous system. NPY and NPY receptors scatter abundantly throughout the arcuate nucleus of the hypothalamus (ARC), the brain area responsible for pain processing. Increases in NPY and Y1 receptor binding lead to decreased pain awareness and increased pain tolerance. Substance P is another neuropeptide that carries pain signals to the central nervous system. Neuropeptide Y blocks the production of Substance P and thus its noxious effects.