Central and peripheral dysregulation of melanin-concentrating hormone in obese Zucker rats

Melanin concentrating hormone (MCH) is a peptide synthesized in the lateral hypothalamus which stimulates food ingestion and leptin secretion in roden ts. In this experiment, we measured the expressions of MCH as well as of it s receptor (SLC-1) in the hypothalamus of obese hyperphagic and lean Zucker rats by quantitative real time RT-PCR. MCH mRNA expression in the obese ra ts was significantly increased by a factor of five (P <0.01) whereas expres sion of SLC-1 was decreased by more than 50% (P <0.05). Circulating levels of leptin and MCH were increased in the plasma of obese Zucker rats when co mpared to lean rats (38-fold and 1.7-fold, respectively, P <0.001 and P <0. 01). However, individual MCH levels were not directly correlated to leptin levels in the lean (functional leptin receptor) or in the obese (non-functi onal leptin receptor) Zucker rats. These results indicate that the absence of leptin signaling in rats is associated with an increased hypothalamic ex pression and circulating release of MCH, contributing to their obesity synd rome. (C) 2001 Elsevier Science BY All rights reserved.