The role of the vagal nerve in peripheral PYY 3-36-induced feeding reduction in rats

Abstract

Peptide YY (PYY), an anorectic peptide, is secreted postprandially from the distal gastrointestinal tract. PYY 3-36, the major form of circulating PYY, binds to the hypothalamic neuropeptide Y Y2 receptor (Y2-R) with a high-affinity, reducing food intake in rodents and humans. Additional gastrointestinal hormones involved in feeding, including cholecystokinin, glucagon-like peptide 1, and ghrelin, transmit satiety or hunger signals to the brain via the vagal afferent nerve and/or the blood stream. Here we determined the role of the afferent vagus nerve in PYY function. Abdominal vagotomy abolished the anorectic effect of PYY 3-36 in rats. Peripheral administration of PYY 3-36 induced Fos expression in the arcuate nucleus of sham-operated rats but not vagotomized rats. We showed that Y2-R is synthesized in the rat nodose ganglion and transported to the vagal afferent terminals. PYY 3-36 stimulated firing of the gastric vagal afferent nerve when administered iv. Considering that Y2-R is present in the vagal afferent fibers, PYY 3-36 could directly alter the firing rate of the vagal afferent nerve via Y2-R. We also investigated the effect of ascending fibers from the nucleus of the solitary tract on the transmission of PYY 3-36-mediated satiety signals. In rats, bilateral mid-brain transections rostral to the nucleus of the solitary tract also abolished PYY 3-36-induced reductions in feeding. This study indicates that peripheral PYY 3-36 may transmit satiety signals to the brain in part via the vagal afferent pathway. Copyright © 2005 by The Endocrine Society.