Exendin-4 Improves Steatohepatitis by Increasing Sirt1 Expression inHigh-Fat Diet-Induced Obese C57BL/6J Mice

Collection with item attached
2012
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/478678.do
DOI
10.1371/journal.pone.0031394
Title
Exendin-4 Improves Steatohepatitis by Increasing Sirt1 Expression inHigh-Fat Diet-Induced Obese C57BL/6J Mice
Description
This study was supported by a grant from Samsung Biomedical ResearchInstitute # C-A8-223-2 (http://www.sbri.or.kr) and Korea Science andEngineering Foundation by the Ministry of Education, Science andTechnology # S-2010-1115-000 (http://www.mest.go.kr). The funders had norole in study design, data collection and analysis, decision to publish,or preparation of the manuscript.
abstract
The effects of exendin-4 on Sirt1 expression as a mechanism of reducing fatty liver have not been previously reported. Therefore, we investigated whether the beneficial effects of exendin-4 treatment on fatty liver are mediated via Sirt1 in high-fat (HF) diet-induced obese C57BL/6J mice and related cell culture models. Exendin-4 treatment decreased body weight, serum free fatty acid (FA), and triglyceride levels in HF-induced obese C57BL/6J mice. Histological analysis showed that exendin-4 reversed HF-induced hepatic accumulation of lipids and inflammation. Exendin-4 treatment increased mRNA and protein expression of Sirt1 and its downstream factor, AMPK, in vivo and also induced genes associated with FA oxidation and glucose metabolism. In addition, a significant increase in the hepatic expression of Lkb1 and Nampt mRNA was observed in exendin-4-treated groups. We also observed increased expression of phospho-Foxo1 and GLUT2, which are involved in hepatic glucose metabolism. In HepG2 and Huh7 cells, mRNA and protein expressions of GLP-1R were increased by exendin-4 treatment in a dose-dependent manner. Exendin-4 enhanced protein expression of Sirt1 and phospho-AMPK alpha in HepG2 cells treated with 0.4 mM palmitic acid. We also found that Sirt1 was an upstream regulator of AMPK in hepatocytes. A novel finding of this study was the observation that expression of GLP-1R is proportional to exendin-4 concentration and exendin-4 could attenuate fatty liver through activation of Sirt1.
provenance
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language
English
author
Lee, Jinmi
Hong, Seok-Woo
Chae, Seoung Wan
Kim, Dong Hoon
Choi, Ji Hun
Bae, Ji Cheol
Park, Se Eun
Rhee, Eun-Jung
Park, Cheol-Young
Oh, Ki-Won
Park, Sung-Woo
Kim, Sun-Woo
Lee, Won-Young
orcid
Rhee, Eun-Jung/0000-0002-6108-7758; LEE, WON-YOUNG/0000-0002-1082-7592
accessioned
2018-09-28T12:39:29Z
available
2018-09-28T12:39:29Z
issued
2012
citation
PLOS ONE(7): 2
issn
1932-6203
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/478678.do
Funder
교육과학기술부
Funding Program
일반연구자지원
Project ID
1345170140
Jurisdiction
Rep.of Korea
Project Name
Study on anti-diabetic action of SIRT1 and NAMPT in beta cell, hepatocyte and adipocyte
rights
openAccess
type
article


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