Exendin-4 Improves Nonalcoholic Fatty Liver Disease by Regulating Glucose Transporter 4 Expression in ob/ob Mice

초록

Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been known to reversehepatic steatosis in ob/ob mice. Although many studies have evaluated molecular targets of Ex-4, itsmechanism of action on hepatic steatosis and fibrosis has not fully been determined. In the liver,glucose transporter 4 (GLUT4) is mainly expressed in hepatocytes, endothelial cells and hepatic stellatecells (HSCs). In the present study, the effects of Ex-4 on GLUT4 expression were determined in theliver of ob/ob mice. Ob/ob mice were treated with Ex-4 for 10 weeks. Serum metabolic parameters,hepatic triglyceride levels, and liver tissues were evaluated for hepatic steatosis. The weights of thewhole body and liver in ob/ob mice were reduced by long-term Ex-4 treatment. Serum metabolicparameters, hepatic steatosis, and hepatic fibrosis in ob/ob mice were reduced by Ex-4. Particularly,Ex-4 improved hepatic steatosis by enhancing GLUT4 via GLP-1R activation in ob/ob mice. Ex-4treatment also inhibited hepatic fibrosis by decreasing expression of connective tissue growth factorin HSCs of ob/ob mice. Our data suggest that GLP-1 agonists exert a protective effect on hepaticsteatosis and fibrosis in obesity and type 2 diabetes.

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