Decreased microsomal triglyceride transfer protein activity contributes to initiation of alcoholic liver steatosis in rats
Decreased microsomal triglyceride transfer protein activity contributes to initiation of alcoholic liver steatosis in rats
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DOI：
10.1016/s0168-8278(01)00263-x
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发表时间：
2002-02-01
影响因子：
25.7
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
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作者：
Sugimoto, T;Yamashita, S;Matsuzawa, Y
背景/目标：为了阐明微粒体甘油三酯转移蛋白（MTP）在酒精性脂肪肝发病机制中的作用，研究了乙醇对MTP活性和基因表达的影响。雄性Sprague-Dawley大鼠分别喂食含乙醇的液体饮食37天，结果显示，与喂食等热量无乙醇饮食的大鼠相比，肝脏胆固醇和甘油三酯含量分别增加了2.9倍和4.9倍（P < 0.01）。此外，在乙醇给药后观察到MTP活性和mRNA表达显著降低（分别降低27%和58%）。静脉注射人重组肝细胞生长因子（hrHGF）的每一个最后7天显着抑制乙醇诱导的肝脏脂质蓄积。hrHGF对脂肪变化的抑制伴随着MTP活性和基因表达的恢复。没有观察到hrHGF对乙醇诱导的酰基辅酶A合成酶活化的抑制作用。使用人肝癌衍生的HepG 2细胞的实验表明，直接的正效应hrHGF对MTP基因表达以及载脂蛋白B secretory.Conclusions：这些结果表明，降低MTP活性是至关重要的酒精性脂肪肝的发展，而促进MTP活性的HGF可能作为一种治疗措施，对酒精性肝脂肪变性。(C)2002年欧洲肝脏研究协会。由Elsevier Science B. V.出版，版权所有。
Background/Aims: To elucidate the role of microsomal triglyceride transfer protein (MTP) in the pathogenesis of alcoholic fatty liver, the effects of ethanol on MTP activity and gene expression were investigated.Methods and results: Male Sprague-Dawley rats fed an ethanol-containing liquid diet for 37 days, respectively, showed 2.9- and 4.9-fold increases in hepatic cholesterol and triglyceride content in comparison with rats fed an isocaloric ethanol-free diet (P < 0.01). Furthermore, a significant decrease in MTP activity and mRNA expression (by 27 and 58%, respectively) was observed after ethanol administration. Intravenous injection of human recombinant hepatocyte growth factor (hrHGF) on each of the last 7 days markedly suppressed ethanol-induced lipid accumulation in the liver. This inhibition of fatty change by hrHGF was accompanied by recovery of MTP activity and gene expression. No inhibitory effect of hrHGF on ethanol-induced acyl-CoA synthetase activation was observed. Experiments using human hepatoma-derived HepG2 cells indicated a direct positive effect of hrHGF on MTP gene expression as well as apolipoprotein B secretion.Conclusions: These results suggest that reduced MTP activity is crucial to development of alcoholic fatty liver, while promotion of MTP activity by HGF might serve as a therapeutic measure against alcoholic liver steatosis. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.