Korean J Physiol Pharmacol.  2014 Aug;18(4):333-339. 10.4196/kjpp.2014.18.4.333.

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

Affiliations
  • 1Department of Anatomy and Convergence Medical Science, Institutes of Health Science, Gyeongsnag National University School of Medicine, Jinju 660-751, Korea. anaroh@gnu.ac.kr
  • 2Department of Internal Medicine, Institutes of Health Science, Gyeongsnag National University School of Medicine, Jinju 660-751, Korea.
  • 3Department of Thoracic and Cardiovascular Surgery, Institutes of Health Science, Gyeongsnag National University School of Medicine, Jinju 660-751, Korea.
  • 4Department of Neurologic Surgery, Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
  • 5Division of Metabolic Diseases, Center for Biomedical Sciences, National Institutes of Health, Cheongwon-gun 363-700, Korea.

Abstract

Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been known to reverse hepatic steatosis in ob/ob mice. Although many studies have evaluated molecular targets of Ex-4, its mechanism 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 stellate cells (HSCs). In the present study, the effects of Ex-4 on GLUT4 expression were determined in the liver 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 the whole body and liver in ob/ob mice were reduced by long-term Ex-4 treatment. Serum metabolic parameters, 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-4 treatment also inhibited hepatic fibrosis by decreasing expression of connective tissue growth factor in HSCs of ob/ob mice. Our data suggest that GLP-1 agonists exert a protective effect on hepatic steatosis and fibrosis in obesity and type 2 diabetes.

Keyword

Exendin-4; Glucose transporter 4; Nonalcoholic fatty liver disease; ob/ob

MeSH Terms

Animals
Connective Tissue Growth Factor
Endothelial Cells
Fatty Liver*
Fibrosis
Glucagon-Like Peptide 1
Glucagon-Like Peptide-1 Receptor
Glucose Transport Proteins, Facilitative*
Hepatic Stellate Cells
Hepatocytes
Liver
Mice*
Obesity
Triglycerides
Weights and Measures
Connective Tissue Growth Factor
Glucagon-Like Peptide 1
Glucose Transport Proteins, Facilitative
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