Evidence for regulated monoacylglycerol acyltransferase expression and activity in human liver

Angela M. Hall, Kou Kou, Zhouji Chen, Terri A. Pietka, Mrudula Kumar, Kevin M. Korenblat, Kyuha Lee, Kay Ahn, Elisa Fabbrini, Samuel Klein, Bryan Goodwin, Brian N. Finck

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Intrahepatic lipid accumulation is extremely common in obese subjects and is associated with the development of insulin resistance and diabetes. Hepatic diacylglycerol and triacylglycerol synthesis predominantly occurs through acylation of glycerol-3-phosphate. However, an alternative pathway for synthesizing diacylglycerol from monoacylglycerol acyltransferases (MGAT) could also contribute to hepatic glyceride pools. MGAT activity and the expression of the three genes encoding MGAT enzymes ( MOGAT1, MOGAT2, and MOGAT3 ) were determined in liver biopsies from obese human subjects before and after gastric bypass surgery. MOGAT expression was also assessed in liver of subjects with nonalcoholic fatty liver disease (NAFLD) or control livers. All MOGAT genes were expressed in liver, and hepatic MGAT activity was readily detectable in liver lysates. The hepatic expression of MOGAT3 was highly correlated with MGAT activity, whereas MOGAT1 and MOGAT2 expression was not, and knockdown of MOGAT3 expression attenuated MGAT activity in a liver-derived cell line. Marked weight loss following gastric bypass surgery was associated with a significant reduction in MOGAT2 and MOGAT3 expression, which were also overexpressed in NAFLD subjects. These data suggest that the MGAT pathway is active and dynamically regulated in human liver and could be an important target for pharmacologic intervention for the treatment of obesity-related insulin resistance and NAFLD.

Original languageEnglish
Pages (from-to)990-999
Number of pages10
JournalJournal of lipid research
Volume53
Issue number5
DOIs
StatePublished - May 2012

Keywords

  • Diacylglycerol
  • Hepatic steatosis
  • Nonalcoholic fatty liver disease
  • Triacylglycerol

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