反油酸处理对人HepG2细胞代谢组的影响
Effect of elaidic acid on the metabolomic changes of human Hep G2 cells
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摘要: 本研究以人细胞(Hep G2)为模型,通过MTT实验研究反油酸对Hep G2细胞存活率的影响,选择1.2 mmol/L和1.5 mmol/L的反式油酸处理Hep G2细胞6和12 h,利用UPLC-MS/MS和GC-MS对Hep G2细胞的代谢组进行检测,以了解人细胞对反式油酸的代谢反应。结果表明,反油酸处理引起了Hep G2细胞代谢水平的广泛变化。反油酸处理促进了脂肪酸合成,引起细胞磷脂代谢显著变化及细胞膜的重构,也增加了胆固醇和酰基甘油代谢中间产物的水平;同时,反油酸引起糖类和氨基酸代谢途径的增强,为脂肪酸合成提供原料。本研究获得的体外代谢组水平的变化为揭示反式脂肪酸与人类健康的不良关系提供了新的证据。Abstract: The human Hep G2 cells were used to investigate the metabolomic responses of Hep G2 cells to the exposure of elaidic acid,with the aim to reveal the molecular mechanisms underlying its harmful effects on human health.Based on the preliminary result of toxicological assay,Hep G2 cells were treated with 1.2 mmol/L and1.5 mmol/L elaidic acid for 6 and 12 h,and the metabolome changes of these cells were analyzed by using a non-targeted platform composing of UPLC-MS/MS and GC-MS.Statistic data revealed that the treatment of elaidic acid resulted in remarkable metabolome changes in Hep G2 cells in a time-dependent way.Elaidic acid treatment accelerated the pathway of fatty acid synthesis,led to the significant changes in phospholipid metabolism,the reconstruction of cell membrane,and the increase of the levels of intermediates involved in cholesterol and acylglycerol metabolism.Eladic acid treatment also enhanced the sugar and amino acid pathways,which provided fuel for the accelerated synthesis of fatty acids. These in vitro metabolomic data provide novel insights into the detrimental effects of trans-fatty acids on human health.