标题：Nuclear receptor PPARγ-regulated monoacylglycerol O-acyltransferase 1 (MGAT1) expression is responsible for the lipid accumulation in diet-induced hepatic steatosis
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：34
页码：13656-13661
DOI：10.1073/pnas.1203218109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Recently, hepatic peroxisome proliferator-activated receptor (PPAR){gamma} has been implicated in hepatic lipid accumulation. We found that the C3H mouse strain does not express PPAR{gamma} in the liver and, when subject to a high-fat diet, is resistant to hepatic steatosis, compared with C57BL/6 (B6) mice. Adenoviral PPAR{gamma}2 injection into B6 and C3H mice caused hepatic steatosis, and microarray analysis demonstrated that hepatic PPAR{gamma}2 expression is associated with genes involved in fatty acid transport and the triglyceride synthesis pathway. In particular, hepatic PPAR{gamma}2 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 PPAR{gamma}2 directly regulates the MGAT1 promoter activity. The MGAT1 overexpression in cultured hepatocytes enhanced triglyceride synthesis without an increase of PPAR{gamma} 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 PPAR{gamma} is critically important in the development of hepatic steatosis during diet-induced obesity.
