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Mitochondrial Glycerol-3-Phosphate Acyltransferase-Deficient Mice Have Reduced Weight and Liver Triacylglycerol Content and Altered Glycerolipid Fatty Acid Composition

机译:线粒体甘油3-磷酸酰基转移酶缺陷型小鼠体重减轻,肝脏三酰甘油含量降低,甘油脂脂肪酸组成改变

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Microsomal and mitochondrial isoforms of glycerol-3-phosphate acyltransferase (GPAT; E.C. 2.3.1.15) catalyze the committed step in glycerolipid synthesis. The mitochondrial isoform, mtGPAT, was believed to control the positioning of saturated fatty acids at the sn-1 position of phospholipids, and nutritional, hormonal, and overexpression studies suggested that mtGPAT activity is important for the synthesis of triacylglycerol. To determine whether these purported functions were true, we constructed mice deficient in mtGPAT. mtGPAT?/? mice weighed less than controls and had reduced gonadal fat pad weights and lower hepatic triacylglycerol content, plasma triacylglycerol, and very low density lipoprotein triacylglycerol secretion. As predicted, in mtGPAT?/? liver, the palmitate content was lower in triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine. Positional analysis revealed that mtGPAT?/? liver phosphatidylethanolamine and phosphatidylcholine had about 21% less palmitate in the sn-1 position and 36 and 40%, respectively, more arachidonate in the sn-2 position. These data confirm the important role of mtGPAT in the synthesis of triacylglycerol, in the fatty acid content of triacylglycerol and cholesterol esters, and in the positioning of specific fatty acids, particularly palmitate and arachidonate, in phospholipids. The increase in arachidonate may be functionally significant in terms of eicosanoid production.
机译:甘油3-磷酸酰基转移酶的微粒体和线粒体同工型(GPAT; E.C. 2.3.1.15)催化甘油脂合成中的重要步骤。线粒体同工型mtGPAT被认为可以控制饱和脂肪酸在磷脂的 sn -1位置上的定位,营养,激素和过表达的研究表明mtGPAT活性对于合成脂蛋白很重要。三酰基甘油。为了确定这些声称的功能是否正确,我们构建了mtGPAT缺陷的小鼠。 mtGPAT ?/?小鼠的体重小于对照组,性腺脂肪垫重量减少,肝三酰甘油含量降低,血浆三酰甘油含量降低,并且脂蛋白三酰甘油的密度非常低。如所预测的,在mtGPAT α/β肝脏中,三酰基甘油,磷脂酰胆碱和磷脂酰乙醇胺中的棕榈酸酯含量较低。位置分析表明,mtGPAT ?/?肝磷脂酰乙醇胺和磷脂酰胆碱在 sn -1位置的棕榈酸酯含量降低约21%,在花生四烯酸中的花生四烯酸酯含量分别提高36%和40%。 sn -2位置。这些数据证实了mtGPAT在三酰甘油的合成,三酰甘油和胆固醇酯的脂肪酸含量以及特定脂肪酸(尤其是棕榈酸酯和花生四烯酸酯)在磷脂中的定位中的重要作用。就类花生酸的产生而言,花生四烯酸酯的增加在功能上可能是重要的。

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