Activation of the NPYY5 receptor regulates both feeding and energy expenditure

Intracerebroventricular (ICV) administration of neuropeptide Y (NPY) has be en shown to decrease energy expenditure, induce hypothermia, and stimulate food intake. Recent evidence has suggested that the Y5 receptor may be a si gnificant mediator of NPY-stimulated feeding. The present study attempts to further characterize the role of NPY Y5-receptor subtypes in feeding and e nergy expenditure regulation. Satiated Long-Evans rats with temperature tra nsponders implanted in the interscapular brown adipose tissue (EAT) display ed a dose-dependent decrease in BAT temperature and an increase in food int ake after ICV infusion of NPY. Similar effects were induced by ICV administ ration of peptide analogs of NPY that activate the Y5 receptor, but not by analogs that activate Y1, Y2, or Y4 receptors. Furthermore, ICV infusion of the Y5 selective agonist D-[Trp(32)]-NPY significantly reduced oxygen cons umption and energy expenditure of rats as measured by indirect calorimetry. These data suggest that the NPY Y5-receptor subtype not only mediates the feeding response of NPY but also contributes to brown fat temperature and e nergy expenditure regulation.