Evidence for regulated monoacylglycerol acyltransferase expression and activity in human liver

被引:75
作者
Hall, Angela M. [1 ]
Kou, Kou [2 ]
Chen, Zhouji [1 ]
Pietka, Terri A. [1 ]
Kumar, Mrudula [1 ]
Korenblat, Kevin M. [1 ]
Lee, Kyuha [2 ]
Ahn, Kay [2 ]
Fabbrini, Elisa [1 ]
Klein, Samuel [1 ]
Goodwin, Bryan [2 ]
Finck, Brian N. [1 ]
机构
[1] Washington Univ, Sch Med, Ctr Human Nutr, St Louis, MO 63110 USA
[2] Pfizer Global Res & Dev, Cardiovasc Metab & Endocrine Dis Res Unit, Groton, CT USA
基金
美国国家卫生研究院;
关键词
hepatic steatosis; triacylglycerol; diacylglycerol; nonalcoholic fatty liver disease; MARKED WEIGHT-LOSS; INSULIN-RESISTANCE; HEPATIC STEATOSIS; LIPID-METABOLISM; FAT-ABSORPTION; OBESE SUBJECTS; DGAT ENZYMES; RAT-LIVER; IDENTIFICATION; BIOSYNTHESIS;
D O I
10.1194/jlr.P025536
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.jlr 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.-Hall, A. M., K. Kou, Z. Chen, T. A. Pietka, M. Kumar, K. M. Korenblat, K. Lee, K. Ahn, E. Fabbrini, S. Klein, B. Goodwin, and B. N. Finck. Evidence for regulated monoacylglycerol acyltransferase expression and activity in human liver. J. Lipid Res. 2012. 53: 990-999.
引用
收藏
页码:990 / 999
页数:10
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