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

作　　者：Yale Duan Rui Zhang Min Zhang Lijuan Sun Suzhen Dong Gang Wang Jun Zhang Zheng Zhao 

机构地区：[1]Key Laboratory of Brain Functional Genomics,Ministry of Education,Shanghai Key Laboratory of Brain Functional Genomics,East China Normal University [2]Department of Clinical Laboratory,Shanghai Public Health Clinical Center Affiliated to Fudan University

出　　处：《Neural Regeneration Research》2013年第25期2379-2388,共10页中国神经再生研究（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China,No.31171019 and No.31200820;the Opening Project of Shanghai Key Laboratory of Brain Functional Genomics and Key Laboratory of Brain Functional Genomics(East China Normal University)of the Ministry of Education

摘　　要：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.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.

关 键 词：neural regeneration METFORMIN food intake body weight gain HYPOTHALAMUS AMP-activated pro-tein kinase neuropeptide Y grants-supported paper NEUROREGENERATION 

分 类 号：R96[医药卫生—药理学]