Eicosapentaenoic acid reduces hepatic synthesis and secretion of triacylglycerol by decreasing the activity of acyl-coenzyme A:1,2-diacylglycerol acyltransferase.
Eicosapentaenoic acid reduces hepatic synthesis and secretion of triacylglycerol by decreasing the activity of acyl-coenzyme A:1,2-diacylglycerol acyltransferase.
复制标题
DOI：
--
复制
发表时间：
1988-11
影响因子：
6.5
通讯作者：
A. C. Rustan;J. Nossen;E. Christiansen;C. Drevon
中科院分区：
文献类型：
--
作者：
A. C. Rustan;J. Nossen;E. Christiansen;C. Drevon
使用培养的实质细胞和来自大鼠肝脏的微粒体，在短期实验中探索了二十碳五烯酸存在下肝脏产生三酰甘油减少的机制。油酸、棕榈酸、硬脂酸和亚油酸是肝细胞三酰[3H]甘油合成和分泌的最有效刺激剂，而芥酸、α-亚麻酸、γ-亚麻酸、花生四烯酸、二十二碳六烯酸和二十碳五烯酸（按递减顺序）刺激性较小。所检测的脂肪酸的三酰基[3H]甘油的合成和分泌之间存在线性相关性（r = 0.85，P小于0.01）。更详细地研究了二十碳五烯酸和油酸对三酰甘油代谢的极端和相反的影响。随着每个白蛋白分子结合的游离脂肪酸分子数量的增加，三酰基[3H]甘油的合成和分泌速率增加，尤其是油酸。两种脂肪酸的细胞摄取相似，但细胞内积累了更多的游离二十碳五烯酸。与油酸相比，二十碳五烯酸导致[3H]水更多地掺入磷脂中，并且更少地掺入三酰甘油和胆固醇酯中。在掺入细胞游离脂肪酸、单酰基甘油和二酰基甘油中的脂肪酸之间没有观察到差异。与二十碳五烯酸相比，在油酸存在下，三酰甘油中一些 16-和 18-碳脂肪酸的含量明显更高。在添加 1,2-二油酰基-甘油的情况下，大鼠肝微粒体将二十碳五烯酸和二十碳五烯酰基-CoA 掺入三酰基甘油中，其程度低于油酸及其 CoA 衍生物。当二十碳五烯酰辅酶A与油酰辅酶A一起给予时，还观察到三酰甘油的形成减少，而棕榈酰辅酶A、硬脂酰辅酶A、亚油酰辅酶A、亚麻酰辅酶A和花生酰辅酶A没有抑制作用。总之，二十碳五烯酸对酰基辅酶A：1,2-二酰基甘油O-酰基转移酶（EC 2.3.1.20）的抑制可能对于减少肝脏三酰基甘油的合成和分泌很重要。
The mechanism for the reduced hepatic production of triacylglycerol in the presence of eicosapentaenoic acid was explored in short-term experiments using cultured parenchymal cells and microsomes from rat liver. Oleic, palmitic, stearic, and linoleic acids were the most potent stimulators of triacyl[3H]glycerol synthesis and secretion by hepatocytes, whereas erucic, alpha-linolenic, gamma-linolenic, arachidonic, docosahexaenoic, and eicosapentaenoic acids (in decreasing order) were less stimulatory. There was a linear correlation (r = 0.85, P less than 0.01) between synthesis and secretion of triacyl[3H]glycerol for the fatty acids examined. The extreme and opposite effects of eicosapentaenoic and oleic acids on triacylglycerol metabolism were studied in more detail. With increasing number of free fatty acid molecules bound per molecule of albumin, the rate of synthesis and secretion of triacyl[3H]glycerol increased, most markedly for oleic acid. Cellular uptake of the two fatty acids was similar, but more free eicosapentaenoic acid accumulated intracellularly. Eicosapentaenoic acid caused higher incorporation of [3H]water into phospholipid and lower incorporation into triacylglycerol and cholesteryl ester as compared to oleic acid. No difference was observed between the fatty acids on incorporation into cellular free fatty acids, monoacylglycerol and diacylglycerol. The amount of some 16- and 18-carbon fatty acids in triacylglycerol was significantly higher in the presence of oleic acid compared with eicosapentaenoic acid. Rat liver microsomes in the presence of added 1,2-dioleoyl-glycerol incorporated eicosapentaenoic acid and eicosapentaenoyl-CoA into triacylglycerol to a lesser extent than oleic acid and its CoA derivative. Decreased formation of triacylglycerol was also observed when eicosapentaenoyl-CoA was given together with oleoyl-CoA, whereas palmitoyl-CoA, stearoyl-CoA, linoleoyl-CoA, linolenoyl-CoA, and arachi-donoyl-CoA had no inhibitory effect. In conclusion, inhibition of acyl-CoA:1,2-diacylglycerol O-acyltransferase (EC 2.3.1.20) by eicosapentaenoic acid may be important for reduced synthesis and secretion of triacylglycerol from the liver.