Original Article

Acta Pharmacologica Sinica (2008) 29, 698–706; doi:10.1111/j.1745-7254.2008.00807.x

Endocrine Pharmacology

Resveratrol improves non-alcoholic fatty liver disease by activating AMP-activated protein kinase

This work was supported by a grant from Key Science-Technology Project of Hubei Province China (No 2007AA301B43).

Jing Shang2, Lu-lu Chen2, Fang-xi Xiao2, Hui Sun2, Hong-cheng Ding2 and Hu Xiao2

2Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

Correspondence: , Fax: 86-27-8535-6365. E-mail: chen_cheria@126.com

Received 17 February 2008; Accepted 2 April 2008.

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Abstract

Aim:

 

To investigate whether resveratrol (RSV) can improve non-alcoholic fatty liver disease (NAFLD) and to find the possible mechanism.

Methods:

 

Rats fed a high-fat diet were treated with RSV. The liver histology was observed. Hyperinsulinemic euglycemic clamp was performed to assess insulin sensitivity. Fat accumulation was induced in HepG2 cells, and the cells were treated with RSV. AMP-activated protein kinase (AMPK) phosphorylation levels were determined both in the animal study and cell study.

Results:

 

Rats fed a high-fat diet developed abdominal obesity, NAFLD, and insulin resistance (IR), which were markedly improved by 10 weeks of RSV administration. RSV treatment prevented triacylglycerol (TG) accumulation in HepG2 cells that were incubated with high concentration of glucose and insulin. Both in vivo and in vitro studies showed that RSV treatment could promote the phosphorylation of AMPK, which in this study, suppressed 2 lipogenesis gene expressions, contributing to the improvement of NAFLD and IR.

Conclusion:

 

The results indicated that by reducing TG accumulation and improving IR, RSV could protect the liver from NAFLD. The activation of AMPK was involved in the mechanism. RSV has the therapeutic potential for preventing or treating NAFLD and IR-related metabolic disorders.

Keywords:

resveratrol, insulin resistance, AMP-activated protein kinase, non-alcoholic fatty liver disease

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