350 725

Cited 0 times in

Nuclear receptor PPARγ-regulated monoacylglycerol O-acyltransferase 1 (MGAT1) expression is responsible for the lipid accumulation in diet-induced hepatic steatosis

Authors
 Yoo Jeong Lee  ;  Eun Hee Ko  ;  Ji Eun Kim  ;  Eunha Kim  ;  Hyemin Lee  ;  Hyeonjin Choi  ;  Jung Hwan Yu  ;  Hyo Jung Kim  ;  Je-Kyung Seong  ;  Kyung-Sup Kim  ;  Jae-woo Kim 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.109(34) : 13656-13661, 2012 
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN
 0027-8424 
Issue Date
2012
MeSH
Acyltransferases/biosynthesis* ; Adenoviridae/genetics ; Animal Feed ; Animals ; Cell Nucleus/metabolism* ; Fatty Liver/metabolism ; Gene Expression Regulation, Enzymologic* ; Lipids/chemistry* ; Male ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Models, Biological ; PPAR gamma/biosynthesis ; PPAR gamma/metabolism* ; Sterol Regulatory Element Binding Protein 1/genetics ; Toll-Like Receptor 4/genetics
Keywords
nonalcoholic fatty liver disease ; adenoviral expression ; SREBP1c ; ChREBP ; TLR4
Abstract
Recently, hepatic peroxisome proliferator-activated receptor (PPAR)γ has been implicated in hepatic lipid accumulation. We found that the C3H mouse strain does not express PPARγ in the liver and, when subject to a high-fat diet, is resistant to hepatic steatosis, compared with C57BL/6 (B6) mice. Adenoviral PPARγ2 injection into B6 and C3H mice caused hepatic steatosis, and microarray analysis demonstrated that hepatic PPARγ2 expression is associated with genes involved in fatty acid transport and the triglyceride synthesis pathway. In particular, hepatic PPARγ2 expression significantly increased the expression of monoacylglycerol O-acyltransferase 1 (MGAT1). Promoter analysis by luciferase assay and electrophoretic mobility shift assay as well as chromatin immunoprecipitation assay revealed that PPARγ2 directly regulates the MGAT1 promoter activity. The MGAT1 overexpression in cultured hepatocytes enhanced triglyceride synthesis without an increase of PPARγ expression. Importantly, knockdown of MGAT1 in the liver significantly reduced hepatic steatosis in 12-wk-old high-fat-fed mice as well as ob/ob mice, accompanied by weight loss and improved glucose tolerance. These results suggest that the MGAT1 pathway induced by hepatic PPARγ is critically important in the development of hepatic steatosis during diet-induced obesity.
Files in This Item:
T201202630.pdf Download
DOI
22869740
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
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
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91749
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links