Novel acyl-coenzyme A: monoacylglycerol acyltransferase plays an important role in hepatic triacylglycerol secretion
Novel acyl-coenzyme A: monoacylglycerol acyltransferase plays an important role in hepatic triacylglycerol secretion
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DOI：
10.1194/jlr.m002584
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发表时间：
2010-06-01
影响因子：
6.5
通讯作者：
Hiramatsu, Ryuji
中科院分区：
文献类型：
--
作者：
Hiramine, Yasushi;Emoto, Hisayo;Hiramatsu, Ryuji
酰基辅酶A：单酰基甘油酰基转移酶(MGAT)在小肠三酰甘油的再合成中起主导作用，但它在其他组织，如肝脏中对三酰甘油合成的作用尚不清楚。在本研究中，我们发现了一个新的MGAT基因，它与溶血磷脂酰甘油酰基转移酶1(LPGAT1)相同。小鼠LPGAT1在许多组织中表达，其中肝脏表达最高。糖尿病db/db小鼠肝脏LPGAT1表达高于对照组db/m小鼠，这与db/db小鼠肝脏MGAT活性升高相一致。为了阐明LPGAT1基因在db/db小鼠脂质代谢中的作用，我们构建了针对LPGAT1的短发夹状RNA(ShRNA)腺病毒，选择性地下调LPGAT1基因在肝脏中的表达。感染LPGAT1 shRNA腺病毒的db/db小鼠肝脏MGAT活性和LPGAT1表达均显著低于对照组。值得注意的是，LPGAT1 shRNA腺病毒治疗导致血清三酰甘油和胆固醇水平显著降低，肝脏胆固醇水平显著上升。这些结果表明，LPGAT1是一种新发现的MGAT酶，在db/db小鼠肝脏三酰甘油的合成和分泌中起着重要作用。新的酰基辅酶A：单酰基甘油酰基转移酶在肝脏三酰甘油分泌中起重要作用。J.Lipid Res.2010年。51：1424-1431
Acyl-CoA:monoacylglycerol acyltransferase (MGAT) plays a predominant role in the resynthesis of triacylglycerol in the small intestine, but its contribution to triacylglycerol synthesis in other tissues, such as the liver, is not clear. In this study, we identified a novel MGAT gene, which is identical with lysophosphatidylglycerol acyltransferase1 (LPGAT1). Mouse LPGAT1 is expressed in a number of tissues and most highly expressed in the liver. Hepatic LPGAT1 expression in diabetic db/db mice is higher than that in the control db/m mouse, which is consistent with increased hepatic MGAT activity in db/db mouse. To elucidate the role of LPGAT1 gene in lipid metabolism in db/db mice, we constructed an adenovirus of short hairpin RNA (shRNA) targeting LPGAT1 to selectively knockdown LPGAT1 gene expression in the liver. Hepatic MGAT activity and LPGAT1 expression in db/db mice infected with LPGAT1 shRNA adenovirus were significantly lower than those in mice infected with the control virus. Notably, treatment with LPGAT1 shRNA adenovirus caused a marked reduction in serum triacylglycerol and cholesterol levels and a significant increase in hepatic cholesterol level. These findings indicate that LPGAT1, a newly identified MGAT enzyme, plays a significant role in hepatic triacylglycerol synthesis and secretion in db/db mice.-Hiramine, Y., H. Emoto, S. Takasuga, and R. Hiramatsu. Novel acyl-coenzyme A: monoacylglycerol acyltransferase plays an important role in hepatic triacylglycerol secretion. J. Lipid Res. 2010. 51: 1424-1431