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Monoacylglycerol O-acyltransferase 1 is regulated by peroxisome proliferator-activated receptor γ in human hepatocytes and increases lipid accumulation

 Jung Hwan Yu  ;  Yoo Jeong Lee  ;  Hyo Jung Kim  ;  Hyeonjin Choi  ;  Yoonjeong Choi  ;  Jo Woon Seok  ;  Jae-woo Kim 
 Biochemical and Biophysical Research Communications, Vol.460(3) : 715-720, 2015 
Journal Title
 Biochemical and Biophysical Research Communications 
Issue Date
Acyltransferases/metabolism* ; Base Sequence ; Cells, Cultured ; DNA Primers ; Electrophoretic Mobility Shift Assay ; Hepatocytes/enzymology* ; Hepatocytes/metabolism ; Humans ; Lipid Metabolism* ; PPAR gamma/metabolism* ; Reverse Transcriptase Polymerase Chain Reaction
Hepatic steatosis ; MGAT1 ; PPARγ ; Primary hepatocytes ; Promoter
Monoacylglycerol O-acyltransferase (MGAT) is an enzyme that is involved in triglyceride synthesis by catalyzing the formation of diacylglycerol from monoacylglycerol and fatty acyl CoAs. Recently, we reported that MGAT1 has a critical role in hepatic TG accumulation and that its suppression ameliorates hepatic steatosis in a mouse model. However, the function of MGAT enzymes in hepatic lipid accumulation has not been investigated in humans. Unlike in rodents, MGAT3 as well as MGAT1 and MGAT2 are present in humans. In this study, we evaluated the differences between MGAT subtypes and their association with peroxisome proliferator-activated receptor γ (PPARγ), a regulator of mouse MGAT1 expression. In human primary hepatocytes, basal expression of MGAT1 was lower than that of MGAT2 or MGAT3, but was strongly induced by PPARγ overexpression. A luciferase assay as well as an electromobility shift assay revealed that human MGAT1 promoter activity is driven by PPARγ by direct binding to at least two regions of the promoter in 293T and HepG2 cells. Moreover, siRNA-mediated suppression of MGAT1 expression significantly attenuated lipid accumulation by PPARγ overexpression in HepG2 cells, as evidenced by oil-red-O staining. These results suggest that human MGAT1 has an important role in fatty liver formation as a target gene of PPARγ, and blocking MGAT1 activity could be an efficient therapeutic way to reduce nonalcoholic fatty liver diseases in humans.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 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)
Choi, Hyeon Jin(최현진)
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