Exendin-4 Improves Nonalcoholic Fatty Liver Disease by Regulating Glucose Transporter 4 Expression in ob/ob Mice.
10.4196/kjpp.2014.18.4.333
- Author:
Seok KIM
1
;
Jaehoon JUNG
;
Hwajin KIM
;
Rok Won HEO
;
Chin Ok YI
;
Jung Eun LEE
;
Byeong Tak JEON
;
Won Ho KIM
;
Jong Ryeal HAHM
;
Gu Seob ROH
Author Information
1. Department of Anatomy and Convergence Medical Science, Institutes of Health Science, Gyeongsnag National University School of Medicine, Jinju 660-751, Korea. anaroh@gnu.ac.kr
- Publication Type:Original Article
- Keywords:
Exendin-4;
Glucose transporter 4;
Nonalcoholic fatty liver disease;
ob/ob
- MeSH:
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
- From:The Korean Journal of Physiology and Pharmacology
2014;18(4):333-339
- CountryRepublic of Korea
- Language:English
-
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.
