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Suppression of PPARγ-mediated monoacylglycerol O-acyltransferase 1 expression ameliorates alcoholic hepatic steatosis.

Authors
 Jung Hwan Yu  ;  Su Jin Song  ;  Ara Kim  ;  Yoonjeong Choi  ;  Jo Woon Seok  ;  Hyo Jung Kim  ;  Yoo Jeong Lee  ;  Kwan Sik Lee  ;  Jae-woo Kim 
Citation
 Scientific Reports, Vol.6 : 29352, 2016 
Journal Title
 Scientific Reports 
ISSN
 2045-2322 
Issue Date
2016
Abstract
Alcohol consumption is one of the major causes of hepatic steatosis, fibrosis, cirrhosis, and superimposed hepatocellular carcinoma. Ethanol metabolism alters the NAD(+)/NADH ratio, thereby suppressing the activity of sirtuin family proteins, which may affect lipid metabolism in liver cells. However, it is not clear how long-term ingestion of ethanol eventually causes lipid accumulation in liver. Here, we demonstrate that chronic ethanol ingestion activates peroxisome proliferator-activated receptor γ (PPARγ) and its target gene, monoacylglycerol O-acyltransferase 1 (MGAT1). During ethanol metabolism, a low NAD(+)/NADH ratio repressed NAD-dependent deacetylase sirtuin 1 (SIRT1) activity, concomitantly resulting in increased acetylated PPARγ with high transcriptional activity. Accordingly, SIRT1 transgenic mice exhibited a low level of acetylated PPARγ and were protected from hepatic steatosis driven by alcohol or PPARγ2 overexpression, suggesting that ethanol metabolism causes lipid accumulation through activation of PPARγ through acetylation. Among the genes induced by PPARγ upon alcohol consumption, MGAT1 has been shown to be involved in triglyceride synthesis. Thus, we tested the effect of MGAT1 knockdown in mice following ethanol consumption, and found a significant reduction in alcohol-induced hepatic lipid accumulation. These results suggest that MGAT1 may afford a promising approach to the treatment of fatty liver disease.
Files in This Item:
T201602267.pdf Download
DOI
10.1038/srep29352
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Woo(김재우) ORCID logo https://orcid.org/0000-0001-5456-9495
Kim, Hyo Jung(김효정) ORCID logo https://orcid.org/0000-0002-3514-1247
Yu, Jung Hwan(유정환)
Lee, Kwan Sik(이관식) ORCID logo https://orcid.org/0000-0002-3672-1198
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/147199
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