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An SOD1 deficiency enhances lipid droplet accumulation in the fasted mouse liver by aborting lipophagy

机译:SOD1缺乏症会通过中止脂肪吞噬而增强禁食小鼠肝脏中脂质滴的积累

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摘要

Under normal feeding conditions, oxidative stress stimulates lipid droplets accumulation in hepatocytes. We found that, despite the low visceral fat in Sod1-knockout (KO) mouse, lipid droplets accumulate in the liver to a greater extent than for the wild-type mouse upon fasting. Liver damage became evident in the KO mice. While fasting caused substantial endoplasmic reticulum stress in KO mice, the expression of genes involved in fatty acid production was suppressed. LC3-II, which is essential for the dynamic process of autophagosome formation, was activated in the wild-type mouse and enhanced in the KO mouse. However, the p62, an adapter protein with the ubiquitin- and LC3-binding activity, accumulated abnormally in the livers of KO mice, implying an abortive lipophagic process as the cause for the impaired lipid metabolism and the hepatic damage that occurs upon fasting. (C) 2015 Elsevier Inc. All rights reserved.
机译:在正常喂养条件下,氧化应激会刺激脂质滴在肝细胞中的积累。我们发现,尽管Sod1基因敲除(KO)小鼠的内脏脂肪较低,但空腹时脂质滴在肝脏中的蓄积比野生型小鼠更大。在KO小鼠中肝损害变得明显。禁食在KO小鼠中引起实质性的内质网应激,同时抑制了脂肪酸产生相关基因的表达。对自噬体形成的动态过程至关重要的LC3-II在野生型小鼠中被激活,在KO小鼠中被增强。但是,p62是一种具有泛素和LC3结合活性的衔接蛋白,在KO小鼠的肝脏中异常蓄积,这暗示着流产的脂肪吞噬过程是脂质代谢受损和禁食时发生的肝损害的原因。 (C)2015 Elsevier Inc.保留所有权利。

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