title: Exendin-4 Improves Nonalcoholic Fatty Liver Disease by Regulating Glucose Transporter 4 Expression in ob/ob Mice.
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.
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institutes of Health Science, Gyeongsnag National University School of Medicine, Jinju 660-751, Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Institutes of Health Science, Gyeongsnag National University School of Medicine, Jinju 660-751, Korea.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Jung
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institutes of Health Science, Gyeongsnag National University School of Medicine, Jinju 660-751, Korea.
authors.forename: Hwajin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institutes of Health Science, Gyeongsnag National University School of Medicine, Jinju 660-751, Korea.
authors.forename: Rok Won
authors.initials: RW
authors.lastname: Heo
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institutes of Health Science, Gyeongsnag National University School of Medicine, Jinju 660-751, Korea.
authors.forename: Chin-Ok
authors.initials: CO
authors.lastname: Yi
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Institutes of Health Science, Gyeongsnag National University School of Medicine, Jinju 660-751, Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Neurologic Surgery, Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Byeong Tak
authors.initials: BT
authors.lastname: Jeon
authors.affiliation: Division of Metabolic Diseases, Center for Biomedical Sciences, National Institutes of Health, Cheongwon-gun 363-700, Korea.
authors.forename: Won-Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Institutes of Health Science, Gyeongsnag National University School of Medicine, Jinju 660-751, Korea.
authors.forename: Jong Ryeal
authors.initials: JR
authors.lastname: Hahm
authors.affiliation: Department of Anatomy and Convergence Medical Science, Institutes of Health Science, Gyeongsnag National University School of Medicine, Jinju 660-751, Korea.
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
keywords: Exendin-4; Glucose transporter 4; Nonalcoholic fatty liver disease; ob/ob