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

• Published in: Acta pharmacologica Sinica Vol. 29; no. 6; pp. 698 - 706
• Main Authors: Shang, Jing, Chen, Lu-lu, Xiao, Fang-xi, Sun, Hui, Ding, Hong-cheng, Xiao, Hu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2008; Nature Publishing Group
• Subjects: AMP; Animals; Antioxidants - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cyclic AMP-Dependent Protein Kinases - metabolism; Diet; Enzyme Activation - drug effects; Fatty Liver - drug therapy; Fatty Liver - pathology; Glucose Clamp Technique; Humans; Hyperinsulinism - metabolism; Immunology; Internal Medicine; Liver - pathology; Male; Medical Microbiology; original-article; Pharmacology/Toxicology; Rats; Stilbenes - therapeutic use; Triglycerides - metabolism; Vaccine; 胰岛素电阻; 蛋白激酶; 非酒精性脂肪肝; non-alcoholic fatty liver disease; AMP-activated protein kinase; resveratrol; insulin resistance
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1111/j.1745-7254.2008.00807.x

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 ceils 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.