DJ-1 Deficiency Protects Hepatic Steatosis by Enhancing Fatty Acid Oxidation in Mice.
DJ-1 Deficiency Protects Hepatic Steatosis by Enhancing Fatty Acid Oxidation in Mice.
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DJ-1 缺乏通过增强小鼠脂肪酸氧化来保护肝脏脂肪变性
DOI：
10.7150/ijbs.28620
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发表时间：
2018
影响因子：
9.2
通讯作者：
Kong X
中科院分区：
文献类型：
--
作者：
Xu M;Wu H;Li M;Wen Y;Yu C;Xia L;Xia Q;Kong X
我们之前的研究表明，DJ-1通过调节肝脏ROS的产生和免疫反应，在肝脏疾病的进展中发挥重要作用，但其在肝脏脂肪变性中的作用仍不清楚。在本研究中，通过采用高脂饮食（HFD）诱导的小鼠模型，我们发现DJ-1敲除（DJ-1-/-）小鼠表现出HFD诱导的肥胖和内脏脂肪积累减少。与这些变化一致，与野生型 (WT) 小鼠相比，DJ-1-/- 小鼠的肝脏重量也有所减轻，肝脏甘油三酯 (TG) 积累也有所改善。 DJ-1-/-小鼠的血糖水平和胰岛素抵抗也有所降低，糖代谢紊乱也有所减轻，而两组小鼠的总胆固醇（TC）和血脂则没有显着差异。从机制上讲，我们发现这两种基因型小鼠的食物摄入量没有差异。此外，脂肪酸合成和糖酵解没有显着差异，但脂肪酸氧化和三羧酸（TCA）循环中的关键酶（如Cpt1α、Pparα、Acox1、Cs、Idh1和Idh2）在DJ-1-/-小鼠肝脏中的表达增加，表明DJ-1-/-小鼠肝脏中脂肪酸氧化和TCA循环增强。我们的数据表明，删除 DJ-1 会增强脂肪酸氧化，导致小鼠肝脏 TG 积累降低，从而保护小鼠肝脏脂肪变性。
Our previous studies have shown that DJ-1 play important roles in progression of liver diseases through modulating hepatic ROS production and immune response, but its role in hepatic steatosis remains obscure. In the present study, by adopting a high-fat-diet (HFD) induced mice model, we found that DJ-1 knockout (DJ-1-/-) mice showing decreased HFD-induced obesity and visceral adipose accumulation. In line with these changes, there were also reduced liver weight and ameliorated hepatic triglyceride (TG) accumulation in DJ-1-/- mice compared to wild-type (WT) mice. And there were also decreased blood glucose levels and insulin resistance and reduced glucose metabolic disorder in DJ-1-/- mice, whereas there were no significant differences in total cholesterol (TC) and serum lipid in two groups of mice. Mechanistically, we found that there were no differences in food intake in these two genotypes of mice. Furthermore, there were no significant differences in fatty acid synthesis and glycolysis, but the expression of key enzymes in fatty acid oxidation and the tricarboxylic acid (TCA) cycle, such as Cpt1α, Pparα, Acox1, Cs, Idh1 and Idh2, was increased in DJ-1-/- mice liver, suggesting that there was enhanced fatty acids oxidation and TCA cycle in DJ-1-/- mice. Our data indicate that deletion of DJ-1 enhancing fatty acids oxidation resulting in lower hepatic TG accumulation in mice, which protecting mice hepatic steatosis.
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DJ-1 缺乏可通过抑制肝脏 ROS 产生和炎症来改善肝纤维化
影响因子：
9.2
作者：
Yu Y;Sun X;Gu J;Yu C;Wen Y;Gao Y;Xia Q;Kong X
通讯作者：
Kong X
影响因子：
9.8
作者：
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通讯作者：
Tsochatzis, Emmanuel A.
影响因子：
4
作者：
Busiello RA;Savarese S;Lombardi A
通讯作者：
Lombardi A
影响因子：
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作者：
Liu, Wenjun;Wu, Hailong;Gao, Wei-Qiang
通讯作者：
Gao, Wei-Qiang
影响因子：
3.7
作者：
Jain D;Weber G;Eberhard D;Mehana AE;Eglinger J;Welters A;Bartosinska B;Jeruschke K;Weiss J;Päth G;Ariga H;Seufert J;Lammert E
通讯作者：
Lammert E