SREBP-1c overexpression induces triglycerides accumulation through increasing lipid synthesis and decreasing lipid oxidation and VLDL assembly in bovine hepatocytes
SREBP-1c overexpression induces triglycerides accumulation through increasing lipid synthesis and decreasing lipid oxidation and VLDL assembly in bovine hepatocytes
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DOI：
10.1016/j.jsbmb.2014.02.009
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发表时间：
2014-09-01
影响因子：
4.1
通讯作者：
Li, Xiaobing
中科院分区：
文献类型：
--
作者：
Li, Xinwei;Li, Yu;Li, Xiaobing
反刍动物脂肪肝的自然发病率明显高于单胃动物。脂肪肝与固醇调节元件结合蛋白1c（SREBP-1c）相关。本研究的目的是调查的调控网络的影响SREBP-1c的脂质代谢基因参与脂肪酸的摄取，激活，氧化，合成，极低密度脂蛋白（VLDL）组装在牛肝细胞。在体外，用腺病毒介导的SREBP-1c过表达载体转染牛肝细胞。SREBP-1c过表达显著上调脂肪酸摄取、活化和合成酶的表达和活性：肝脏脂肪酸结合蛋白、脂肪酸移位酶、酰基辅酶A合成酶长链1、乙酰辅酶A羧化酶1和脂肪酸合成酶，增加甘油三酯（TG）的合成和积累。SREBP-1c过表达下调脂质氧化酶的表达和活性：肉毒碱棕榈酰转移酶1和肉毒碱棕榈酰转移酶2。此外，载脂蛋白B100的表达和微粒体甘油三酯转移蛋白的活性显着降低。SREBP-1c过表达减少脂质氧化和VLDL合成，从而减少TG的处置和输出。因此，大量TG在牛肝细胞中积累。总之，这些结果表明，SREBP-1c过表达增加脂质合成，减少脂质氧化和VLDL输出，从而诱导TG在牛肝细胞中的积累。(C)2014爱思唯尔有限公司版权所有。
The natural incidence of fatty liver in ruminants is significantly higher than in monogastric animals. Fatty liver is associated with sterol regulatory element-binding protein 1c (SREBP-1c). The aim of this study was to investigate the regulatory network effects of SREBP-1c on the lipid metabolic genes involved in fatty acid uptake, activation, oxidation, synthesis, and very low-density lipoprotein (VLDL) assembly in bovine hepatocytes. In vitro, bovine hepatocytes were transfected with an adenovirus-mediated SREBP-1c overexpression vector. SREBP-1c overexpression significantly up-regulated the expression and activity of the fatty acid uptake, activation, and synthesis enzymes: liver fatty acid binding protein, fatty acid translocase, acyl-CoA synthetase long-chain 1, acetyl-CoA carboxylase 1, and fatty acid synthase, increasing triglyceride (TG) synthesis and accumulation. SREBP-1c overexpression down-regulated the expression and activity of the lipid oxidation enzymes: carnitine palmitoyltransferase 1 and carnitine palmitoyltransferase 2. Furthermore, the apolipoprotein B100 expression and microsomal triglyceride transfer protein activity were significantly decreased. SREBP-1c overexpression reduced lipid oxidation and VLDL synthesis, thereby decreasing TG disposal and export. Therefore, large amounts of TG accumulated in the bovine hepatocytes. Taken together, these results indicate that SREBP-1c overexpression increases lipid synthesis and decreases lipid oxidation and VLDL export, thereby inducing TG accumulation in bovine hepatocytes. (C) 2014 Elsevier Ltd. All rights reserved.