Prevention Mechanism of 2,3,5,4'-Tetrahydroxy-stilbene-2-O-β-D-glucoside on Lipid Accumulation in Steatosis Hepatic L-02 Cell.
Prevention Mechanism of 2,3,5,4'-Tetrahydroxy-stilbene-2-O-β-D-glucoside on Lipid Accumulation in Steatosis Hepatic L-02 Cell.
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DOI：
10.4103/0973-1296.204563
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发表时间：
2017-04
影响因子：
0.7
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Lin P;Lu JM;Wang YF;Gu W;Zhao RH;Yu J
2，3，5，4 '-四羟基二苯乙烯-2-O-β-d-葡萄糖苷（TSG）是一种天然二苯乙烯类化合物，具有良好的调脂活性，尤其是降肝甘油三酯活性。然而，关于其对甘油三酯的生物合成和降解机制的信息仍然有限。本研究旨在阐明TSG预防肝脏脂质蓄积的作用机制。TSG对脂肪乳诱导的L-02细胞脂肪变性有明显的抑制作用。在有或没有TSG暴露的情况下，测定了在甘油三酯生物合成和分解中起关键作用的游离脂肪酸、甘油三酯、速率控制酶和转录调节因子的含量。TSG可减少内源性甘油三酯合成所需的游离脂肪酸物质供应，其作用机制是通过降低肝型脂肪酸结合蛋白和脂肪酸转运蛋白4的表达。TS G抑制了甾醇调节元件结合蛋白1c的表达，进而降低了乙酰辅酶A羧化酶1和脂肪酸合成酶的含量。因此，TSG阻止甘油三酯的生物合成。同时，TSG还通过激活过氧化物酶体增殖物激活剂受体α促进甘油三酯的分解。TSG能有效地干预肝细胞内甘油三酯的蓄积。因此，TSG有望成为防治脂质代谢紊乱，特别是非酒精性脂肪肝的候选药物。使用的缩略语：ACACA：乙酰辅酶A羧化酶1，载脂蛋白B100：载脂蛋白B100，脂肪酸合成酶：脂肪酸合成酶，脂肪酸转运蛋白4，胎牛血清：胎牛血清; FEN：非诺贝特，游离脂肪酸，L-FABP：肝型脂肪酸结合蛋白，脂蛋白脂酶：脂蛋白脂酶，微粒体甘油三酯转移蛋白，非酒精性脂肪肝，PBS：磷酸盐缓冲盐水，过氧化物酶体增殖物激活受体-α：过氧化物酶体增殖物激活剂受体α，RPMI：罗斯威尔公园纪念研究所，SIM：辛伐他汀，SREBF 1c：固醇调节元件结合蛋白1c，TG：甘油三酯，TSG：2，3，5，4-四羟基-二苯乙烯-2-O-β-D葡萄糖苷，VLDL：极低密度脂蛋白。
2,3,5,4’-Tetrahydroxy-stilbene-2-O-β-d-glucoside (TSG), a natural stilbene, shows great activities in hepatic lipid regulation, especially for hepatic triglyceride lowering. However, information about its mechanisms on biosynthesis and degradation of triglyceride is still limited. This research pays close attention to clarify the mechanism of TSG on prevention of hepatic lipid accumulation. TSG was given to steatosis hepatocyte L-02 cell induced by fat emulsion incubation. The contents of free fatty acid, triglyceride, rate-controlling enzymes, and transcriptional regulatory factors, which play key role in biosynthesis and decomposition of triglyceride, were determined with or without TSG exposure. TSG could reduce the free fatty acid material supply for the synthesis of endogenous triglyceride and it did so by reducing the expression of liver type fatty acid binding protein and fatty acid transport protein 4. TS Ginhibited the expression of sterol regulatory element-binding protein 1c, and then reduce the contents of acetyl-CoA carboxylase 1 and fatty acid synthase. Therefore, TSG prevented biosynthesis of triglyceride. Mean while, TSG also promoted the decomposition of triglyceride by the activation of peroxisome proliferators activator receptors alpha. TSG could effective intervene the accumulation of triglyceride in hepatic cell. Thus, TSG could be considered as a promising drug candidate in prevention and treatment of lipid metabolic disorders, especially nonalcoholic fatty liver disease. Abbreviations Used: ACACA: Acetyl-CoA carboxylase 1, Apo-B100: Apo lipoprotein B100, FASN: Fatty acid synthase, FATP4: Fatty acid transport protein 4, FBS: Fetal bovine serum; FEN: Fenofibrate, FFA: Free fatty acid, L-FABP: Liver type fatty acid binding protein, LPL: Lipoprotein lipase, MTTP: Microsomal triglyceride transfer protein, NAFLD: Non-alcoholic fatty liver disease, PBS: Phosphate buffer saline, PPAR-α: Peroxisome proliferators activator receptors alpha, RPMI: Roswell Park Memorial Institute, SIM: Simvastatin, SREBF1c: Sterol regulatory element-binding protein 1c, TG: Triglyceride, TSG: 2, 3, 5, 4-tetrahydroxy-stilbene-2-O-β-Dglucoside, VLDL: Very low density lipoprotein.