Quercetin inhibits fatty acid and triacylglycerol synthesis in rat-liver cells
Quercetin inhibits fatty acid and triacylglycerol synthesis in rat-liver cells
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DOI：
10.1111/j.1365-2362.2009.02167.x
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发表时间：
2009-09-01
影响因子：
5.5
通讯作者：
Siculella, L.
中科院分区：
文献类型：
--
作者：
Gnoni, G. V.;Paglialonga, G.;Siculella, L.
背景：由于具有抗氧化能力和调节血脂异常的能力，栎皮素具有心血管保护作用。由于肝脏脂质合成的改变是调节血脂水平的关键，因此我们研究了槲皮素对大鼠肝细胞脂肪生成的影响。材料与方法在[1-C-14]乙酸酯掺入大鼠肝细胞悬液中，观察了槲皮素对脂肪酸、胆固醇、中性脂、磷脂和极低密度脂蛋白(VLDL)合成速率的影响。在洋地黄素通透性肝细胞中，分别检测乙酰辅酶A羧化酶(ACC)、脂肪酸合成酶(Fas)、二酰甘油酰基转移酶(DGAT)和3-羟基-3-甲基-戊二酰辅酶A还原酶(HMG-CoA-R)的活性，以及从头合成脂肪酸、三酰甘油(TAG)和胆固醇合成的控制步骤。观察到主要掺入标签的标签减少。在新合成的脂肪酸中，棕榈酸的形成大大减少，这表明从头合成脂肪的酶步骤(S)受到了影响。仅ACC活性显著降低，而Fas活性无明显变化。DGAT活性也受到抑制。细胞内标签含量的减少与醋酸盐掺入极低密度脂蛋白标签的减少是平行的。结论在正常大鼠肝细胞中，槲皮素诱导的从头合成脂肪酸和TAG合成均减少，从而减少VLDL-Tag的形成，这可能是其降三酰甘油作用的一个潜在机制。
BackgroundQuercetin plays a cardiovascular protective role because of its antioxidant capacity and ability to modulate dyslipidemia. As alterations in hepatic lipid synthesis are crucial to the regulation of serum lipid levels, we investigated the quercetin effect on lipogenesis in rat liver cells.Materials and methodsThe effect of quercetin on the rate of synthesis of fatty acids, cholesterol, neutral lipids, phospholipids and very-low-density lipoproteins (VLDL) was investigated in rat hepatocyte suspensions following [1-C-14]acetate incorporation into these lipid fractions. Enzyme activities of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) as well as diacylglycerol acyltransferase (DGAT) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA-R), pace-setting steps of de novo fatty acid, triacylglycerol (TAG) and cholesterol synthesis respectively were assayed in digitonin-permeabilized hepatocytes.ResultsWithin 30 min of quercetin addition to the hepatocytes, inhibition (IC50 similar to 25 mu M) of fatty acid synthesis occurred. A reduction in label incorporation mainly into TAG was observed. Among neosynthesized fatty acids, palmitic acid formation was greatly reduced, suggesting that enzymatic step(s) of de novo fatty synthesis was affected. Only ACC activity was noticeably reduced, but no change in FAS activity was observed. DGAT activity was also inhibited. The decreased intracellular TAG content was paralleled by a reduction in acetate incorporation into VLDL-TAG. Conversely, cholesterol synthesis and HMG-CoA-R were not significantly affected by quercetin.ConclusionsIn hepatocytes from normal rats, the quercetin-induced decrease in both de novo fatty acid and TAG synthesis, with a consequent reduction in VLDL-TAG formation, may represent a potential mechanism contributing to the reported hypotriacylglycerolemic effect of quercetin.