NPY (Neuropeptide Y)

Neuropeptide Y is the most abundant peptide released from the hypothalamus and it is found not only in the brain, but also in the autonomic nervous system. Thirty-six amino acid residues including a tyrosine at each end make up the structure of NYP. NYP [Page 514]is known to be one of the most potent stimulators of food intake. Not only does NPY function in feeding behavior, but it also functions in several other physiologic roles such as circadian rhythms, sexual function, anxiety responses, vascular resistance, memory and learning, and epilepsy. There is evidence to suggest that NPY is also involved in the regulation of feeding behavior including food intake and carbohydrate preference as well as metabolic and lipogenic rates. Therefore, NPY may be involved in regulation of body fat and development of obesity.

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). The lipostat system is a system whereby our energy stores generate signals that are compared with targets encoded in the brain, and differences between these drive our food intake levels, activity patterns, and resting and active metabolisms. In relation to feeding, 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. The arcuate nucleus is a collection of neurons (nerve cells) in the hypothalamus of the brain. Increased arcuate nucleus activity acts on the paraventricular nucleus to inhibit the production of NPY at that site, thus reducing feeding behavior. Arcuate nucleus activity also stimulates the release of CRH which further decreases feeding and increases energy expenditure.

NPY operates on the G-protein coupled receptor. This kind of receptor causes metabolic changes in the target cell. It contains seven membrane spanning domains and five subtypes. Four of the five subtypes are functional in humans. Subtype Y1 and Y5 have known roles in the stimulation of feeding and Y2 and Y4 have known roles in inhibiting appetite.

Injection of NPY into cerebral ventricles or directly into the hypothalamus of rats potently stimulates food intake and decreases energy expenditure, while simultaneously inducing lipogenic enzymes in liver and white adipose tissue. Consequently, continuous or repeated central administration of NPY leads readily to obesity.