Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory for Molecular Imaging, Collaborative Research Center, Shanghai University of Medicine & Health Science, Shanghai, China.
Int J Biol Sci. 2018 Oct 20;14(13):1892-1900. doi: 10.7150/ijbs.28620. eCollection 2018.
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 and , 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.
我们之前的研究表明，DJ-1 通过调节肝内 ROS 产生和免疫反应，在肝脏疾病的进展中发挥重要作用，但它在肝脂肪变性中的作用尚不清楚。在本研究中，我们通过采用高脂肪饮食（HFD）诱导的小鼠模型发现，DJ-1 敲除（DJ-1 ）小鼠表现出 HFD 诱导的肥胖和内脏脂肪堆积减少。与这些变化一致，与野生型（WT）小鼠相比，DJ-1 小鼠的肝重和肝内甘油三酯（TG）蓄积也有所改善。DJ-1 小鼠的血糖水平和胰岛素抵抗降低，葡萄糖代谢紊乱减轻，而两组小鼠的总胆固醇（TC）和血清脂质无明显差异。从机制上讲，我们发现这两种基因型的小鼠的进食量没有差异。此外，脂肪酸合成和糖酵解没有显著差异，但 DJ-1 小鼠肝脏中脂肪酸氧化和三羧酸（TCA）循环的关键酶，如 和 的表达增加，表明 DJ-1 小鼠的脂肪酸氧化和 TCA 循环增强。我们的数据表明，DJ-1 的缺失增强了脂肪酸的氧化，导致小鼠肝内 TG 蓄积减少，从而保护了小鼠的肝脂肪变性。
