Metformin inhibits food intake and neuropeptide Y gene expression in the hypothalamus

Neural Regen Res. 2013 Sep 5;8(25):2379-88. doi: 10.3969/j.issn.1673-5374.2013.25.009.

Abstract

Metformin may reduce food intake and body weight, but the anorexigenic effects of metformin are still poorly understood. In this study, Sprague-Dawley rats were administered a single intracere-broventricular dose of metformin and compound C, in a broader attempt to investigate the regula-tory effects of metformin on food intake and to explore the possible mechanism. Results showed that central administration of metformin significantly reduced food intake and body weight gain, par-ticularly after 4 hours. A reduction of neuropeptide Y expression and induction of AMP-activated protein kinase phosphorylation in the hypothalamus were also observed 4 hours after metformin administration, which could be reversed by compound C, a commonly-used antagonist of AMP-activated protein kinase. Furthermore, metformin also improved lipid metabolism by reducing plasma low-density lipoprotein. Our findings suggest that under normal physiological conditions, central regulation of appetite by metformin is related to a decrease in neuropeptide Y gene expres-sion, and that the activation of AMP-activated protein kinase may simply be a response to the anorexigenic effect of metformin.

Keywords: AMP-activated protein kinase; body weight gain; food intake; grants-supported paper; hypothalamus; metformin; neural regeneration; neuropeptide Y; neuroregeneration.