Mitochondrial stress protein HSP60 regulates ER stress-induced hepatic lipogenesis

Mitochondrial stress protein HSP60 regulates ER stress-induced hepatic lipogenesis
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线粒体应激蛋白 HSP60 调节 ER 应激诱导的肝脏脂肪生成

DOI:
10.1530/jme-19-0207
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发表时间:
2019-12
影响因子:
3.5
通讯作者:
Hu F
Hu F
中科院分区:
医学3区
文献类型:
--
作者:
Xiao T;Liang X;Liu H;Zhang F;Meng W;Hu F

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内质网应激和线粒体功能障碍与肝脏脂肪变性和胰岛素抵抗有关。内质网应激和/或线粒体功能障碍导致代谢紊乱和肝脂肪变性的分子机制仍有待充分了解。本研究发现,高脂饮食(HFD)或化学诱导内质网应激可刺激小鼠肝细胞线粒体应激蛋白HSP60表达,损害线粒体呼吸,降低线粒体膜电位。HSP60过表达可促进小鼠肝细胞内质网应激和肝脂质蛋白表达,并损害胰岛素信号。机制上,HSP60通过mTORC1-SREBP1信号通路调节内质网应激诱导的肝脏脂肪生成。这些结果表明,HSP60是内质网和线粒体应激交叉对话的重要蛋白,可能控制内质网应激诱导的肝脏脂肪生成和胰岛素抵抗。
Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are associated with hepatic steatosis and insulin resistance. Molecular mechanisms underlying ER stress and/or mitochondrial dysfunction that cause metabolic disorders and hepatic steatosis remain to be fully understood. Here, we found that a high fat diet (HFD) or chemically induced ER stress can stimulate mitochondrial stress protein HSP60 expression, impair mitochondrial respiration, and decrease mitochondrial membrane potential in mouse hepatocytes. HSP60 overexpression promotes ER stress and hepatic lipogenic protein expression and impairs insulin signaling in mouse hepatocytes. Mechanistically, HSP60 regulates ER stress-induced hepatic lipogenesis via the mTORC1-SREBP1 signaling pathway. These results suggest that HSP60 is an important ER and mitochondrial stress cross-talking protein and may control ER stress-induced hepatic lipogenesis and insulin resistance.
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发表时间: 2003-10
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