The Feeding Response to Melanin-Concentrating Hormone Is Attenuated by Antagonism of the NPY Y1-Receptor in the Rat

Publisher Website
Google Scholar
Abstract
Melanin-concentrating hormone (MCH) and NPY are orexi- genic peptides localized in the lateral hypothalamic area and arcuate nucleus, respectively. Although both NPY- and MCH- containing fibers innervate areas of the hypothalamus impli- cated in feeding, the extent to which the regulation of appetite is dependent on interactions between these peptides is un- known. Daytime feeding responses to 2 nmol MCH, 1 nmol NPY, or vehicle were investigated in male Sprague Dawley rats previously implanted with intracerebroventricular can- nulas. The effects of prior administration of the Y1-receptor antagonists BIBO 3304 (20 nmol) or GR231118 (5 nmol) on these responses were examined. NPY and MCH stimulated food intake relative to vehicle (4 h intake, 5.9 0.7 and 3.6 0.2 g, respectively; P < 0.0001). BIBO 3304 and GR231118 significantly inhibited MCH- induced feeding by 73% (P < 0.01) and 86% (P < 0.01), respec- tively, at 2 h. Coadministration of NPY and MCH did not in- crease food intake above that in response to NPY alone; how- ever, prior administration of BIBO 3304 resulted in a less marked inhibition of feeding (P < 0.05, 30 min only). Inhibition of MCH-induced feeding by two structurally dif- ferent NPY Y1-receptor antagonists provides strong evidence that the orexigenic action of MCH involves the Y1-receptor. (Endocrinology 143: 191-197, 2002) T HE REGULATION OF appetite is a highly integrated system involving numerous central and peripheral reg- ulators, reflecting the complex nature of energy homeostasis. The hypothalamus is a key feeding center within the central nervous system (CNS), and many hypothalamic neuropep- tides, such as NPY and melanin-concentrating hormone (MCH), play a pivotal role in the regulation of food intake (1). Due to the intricate network of neuropeptide signaling path- ways involved, the mechanisms underlying the regulation of food intake and energy expenditure are not completely understood. NPY is the most potent endogenous stimulator of feeding known, with the intracerebroventricular (icv) administration of nanomole quantities eliciting eating in satiated rats (2). Furthermore, chronic administration of NPY causes hy- perphagia and an increase in body weight, resulting in obe- sity (3). NPY mRNA is markedly increased in the hypothal- amus of genetically obese animals (4). Thus, the factors regulating this potent feeding stimulator may have impor- tant implications in the therapeutic management of obesity. NPY-containing fibers are widely distributed throughout the CNS, and within the hypothalamus NPY is particularly abundant in the paraventricular nucleus (PVN) (5), an area important in the control of eating behavior that receives a dense NPY-containing projection from the arcuate nucleus (6). Studies in vivo have demonstrated that NPY release in the PVN is strongly associated with increased appetite (7), and central administration of NPY increases c-fos expression in this region (8).

This publication has 0 references indexed in Scilit: