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Resveratrol ameliorates lipid accumulation in HepG2 cells, associated with down-regulation of lipin1 expression

机译:白藜芦醇改善HepG2细胞中的脂质蓄积,与下调lipin1表达有关

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The pathogenesis of alcoholic fatty liver (AFL) disease is associated with the excessive accumulation of lipids in hepatocytes as well as oxidative stress. Resveratrol (RES), a dietary polyphenol found in red wine and grapes, has been shown to protect against AFL disease. However, the precise mechanisms that lead to this protective effect remain elusive. In this study, we used HepG2 cells to investigate the effects of RES on lipid metabolism and the mechanisms underlying these effects. HepG2 cells were cultured with oleic acid and alcohol for 48 h to induce excessive lipid accumulation. Oil red O staining showed that administration of oleic acid and alcohol induced more lipid accumulation than was observed in the control group, and that RES (15, 45, or 135 mu mol/L) treatment reduced intracellular lipid droplets. RES treatment also significantly attenuated hepatic steatosis and lowered levels of intracellular triglycerides (TG). Western blot analysis showed that RES enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and down-regulated the expression of sterol regulatory element-binding protein 1c (SREBP-1c) and lipin1. However, compound C, an AMPK inhibitor, reversed these effects of RES. In conclusion, RES reduced lipid accumulation and protected HepG2 cells. This effect may be associated with the down-regulation of SREBP-1c and lipin1 expression, increased levels of phosphorylated AMPK and ACC, and the activation of AMPK-lipin1 signaling.
机译:酒精性脂肪肝(AFL)疾病的发病机理与脂质在肝细胞中的过度积累以及氧化应激有关。白藜芦醇(RES)是一种在红酒和葡萄中发现的膳食多酚,已被证明可以预防AFL疾病。但是,导致这种保护作用的确切机制仍然难以捉摸。在这项研究中,我们使用了HepG2细胞来研究RES对脂质代谢的影响以及这些作用的潜在机制。将HepG2细胞与油酸和酒精培养48小时,以诱导脂质过多积聚。油红O染色显示,与对照组相比,油酸和酒精的给药引起更多的脂质蓄积,并且RES(15、45或135μmol/ L)处理减少了细胞内脂质滴。 RES治疗还显着减轻了肝脂肪变性并降低了细胞内甘油三酸酯(TG)的水平。 Western印迹分析表明,RES增强了AMP激活的蛋白激酶(AMPK)和乙酰辅酶A羧化酶(ACC)的磷酸化,并下调了固醇调节元件结合蛋白1c(SREBP-1c)和lipin1的表达。但是,化合物C(一种AMPK抑制剂)可以逆转RES的这些作用。总之,RES减少脂质积累并保护HepG2细胞。这种作用可能与SREBP-1c和lipin1表达的下调,磷酸化AMPK和ACC的水平升高以及AMPK-lipin1信号的激活有关。

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