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Estrogen-related Receptor γ Controls Sterol Regulatory Element-Binding protein-1c Expression and Alcoholic Fatty Liver

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Author(s)
Don-Kyu KimYong-Hoon KimJae-Ho LeeYoon Seok JungJina KimRilu FengTae-Il JeonIn-Kyu LeeSung Jin ChoSeung-Soon ImSteven DooleyTimothy F. OsborneChul-Ho LeeHueng-Sik Choi
Keimyung Author(s)
Lee, Jae Ho
Department
Dept. of Anatomy (해부학)
Journal Title
Biochimica et biophysica acta. Molecular and cell biology of lipids
Issued Date
2019
Volume
1864
Issue
12
Keyword
ERRγSREBP-1cCB1 receptorGene regulationHepatic lipogenesisAlcoholic fatty liver
Abstract
Although SREBP-1c regulates key enzymes required for hepatic de novo lipogenesis, the mechanisms underlying transcriptional regulation of SREBP-1c in pathogenesis of alcoholic fatty liver is still incompletely understood. In this study, we investigated the role of ERRgamma in alcohol-mediated hepatic lipogenesis and examined the possibility to ameliorate alcoholic fatty liver through its inverse agonist. Hepatic ERRgamma and SREBP-1c expression was increased by alcohol-mediated activation of CB1 receptor signaling. Deletion and mutation analyses of the Srebp-1c gene promoter showed that ERRgamma directly regulates Srebp-1c gene transcription via binding to an ERR-response element. Overexpression of ERRgamma significantly induced SREBP-1c expression and fat accumulation in liver of mice, which were blocked in Srebp-1c-knockout hepatocytes. Conversely, liver-specific ablation of ERRgamma gene expression attenuated alcohol-mediated induction of SREBP-1c expression. Finally, an ERRgamma inverse agonist, GSK5182, significantly ameliorates fatty liver disease in chronically alcohol-fed mice through inhibition of SREBP-1c-mediated fat accumulation. ERRgamma mediates alcohol-induced hepatic lipogenesis by upregulating SREBP-1c expression, which can be blunted by the inverse agonist for ERRgamma, which may be an attractive therapeutic strategy for the treatment of alcoholic fatty liver disease in human.
Keimyung Author(s)(Kor)
이재호
Publisher
School of Medicine (의과대학)
Citation
Don-Kyu Kim et al. (2019). Estrogen-related Receptor γ Controls Sterol Regulatory Element-Binding protein-1c Expression and Alcoholic Fatty Liver. Biochimica et biophysica acta. Molecular and cell biology of lipids, 1864(12), 158521–158521. doi: 10.1016/j.bbalip.2019.158521
Type
Article
ISSN
1879-2618
Source
http://www.informatics.jax.org/reference/31479733
DOI
10.1016/j.bbalip.2019.158521
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/42313
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Anatomy (해부학)
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