Laboratory of Laboratory/Sports Medicine, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Ibaraki, Japan.
Master's Program in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Ibaraki, Japan.
Int J Mol Sci. 2021 May 29;22(11):5851. doi: 10.3390/ijms22115851.
The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports on the effects on mice of being fed a CDAHFD for long periods of 1 to 3 months. However, the effect of this diet over a short period is unknown. Therefore, we examined the effect of 1-week CDAHFD feeding on the mouse liver. Feeding a CDAHFD diet for only 1-week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis or cirrhosis. Additionally, it was demonstrated that CDAHFD significantly impaired mitochondrial respiration with severe oxidative stress to the liver, which is associated with a decreasing mitochondrial DNA copy number and complex proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that 1 week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of NASH in humans.
非酒精性脂肪性肝病（NAFLD）的患病率在全球范围内迅速上升。胆碱缺乏、L-氨基酸定义的高脂肪饮食（CDAHFD）已被用于创建非酒精性脂肪性肝炎（NASH）的小鼠模型。有一些关于长期（1 至 3 个月）给予 CDAHFD 对小鼠影响的报道。然而，这种饮食在短时间内的效果尚不清楚。因此，我们检查了 1 周 CDAHFD 喂养对小鼠肝脏的影响。仅用 CDAHFD 喂养 1 周就会导致肝脏内脂质滴沉积，并增加血浆中肝脏来源酶的活性。另一方面，它不会引起纤维化或肝硬化。此外，研究表明 CDAHFD 会严重损害线粒体呼吸功能，并导致肝脏严重氧化应激，这与线粒体 DNA 拷贝数和复合蛋白减少有关。在肝脏的基因表达分析中，CDAHFD 显著增加了炎症和氧化应激标志物。这些结果表明，用 CDAHFD 喂养小鼠 1 周可诱导具有线粒体功能障碍和严重氧化应激的脂肪性肝炎，而没有纤维化，这可以部分模拟人类 NASH 的早期阶段。
