Apoptosis‐inducing factor (AIF) is a mitochondrial flavoprotein involved in redox signalling and programmed cell death. The role of AIF has been well recognized in diabetes and obesity. However, the aspect of AIF deficiency in the development of hepatic steatosis and liver injury is unknown. Therefore, in the current study, Harlequin (Hq mutant) mouse with markedly reduced content of AIF was investigated to explore the role of AIF on the initiation of liver injury. The wild type (WT) developed physiological and pathological features of non‐alcoholic fatty liver disease (NAFLD) that were not seen in the Hq mice with AIF deficiency, when fed on high fat high fructose (HFHF) diet. Following bile duct ligation (BDL), the liver associated pathological changes were less conspicuous in Hq mice as compared to WT mice. The expression of AIF protein and apoptosis was markedly lesser as compared to their respective control in Hq mice on HFHF diet. Furthermore, the genes involved in fatty acid metabolism were also altered in the group of treated Hq mice. In conclusion, Hq mice failed to develop diet induced hepatic steatosis, suggestive of a role of AIF mediated pathway in the initiation and progression of liver inflammation. Thus, partial loss of AIF appears to be hepatoprotective.

中文翻译：

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在高脂肪高果糖饮食或胆管结扎的情况下，凋亡诱导因子不足的小鼠未能发展为肝脂肪变性

凋亡诱导因子（AIF）是一种线粒体黄素蛋白，参与氧化还原信号传导和程序性细胞死亡。在糖尿病和肥胖症中，AIF的作用已得到公认。然而，在肝脂肪变性和肝损伤的发展中AIF缺乏的方面是未知的。因此，在当前的研究中，对具有明显降低的AIF含量的Harlequin（Hq突变体）小鼠进行了研究，以探讨AIF在引发肝损伤中的作用。以高脂高果糖（HFHF）饮食喂养时，野生型（WT）出现了非酒精性脂肪肝疾病（NAFLD）的生理和病理特征，这在AIF缺乏的Hq小鼠中没有出现。胆管结扎（BDL）后，与WT小鼠相比，Hq小鼠的肝脏相关病理变化不那么明显。在HFHF饮食的Hq小鼠中，与它们各自的对照相比，AIF蛋白的表达和凋亡明显更少。此外，在治疗过的Hq小鼠组中，与脂肪酸代谢有关的基因也发生了改变。总之，Hq小鼠未能发展饮食引起的肝脂肪变性，提示AIF介导的途径在肝炎症的发生和发展中发挥了作用。因此，AIF的部分丢失似乎具有肝保护作用。