Toita Riki, Kang Jeong-Hun
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka, 563-8577, Japan; AIST-Osaka University Advanced Photonics and Biosensing Open Innovation Laboratory, AIST, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Division of Biopharmaceutics and Pharmacokinetics, National Cerebral and Cardiovascular Center Research Institute, 6-1 Shinmachi, Kishibe, Suita, Osaka, 564-8565, Japan.
Toxicol Lett. 2020 Oct 10;332:1-6. doi: 10.1016/j.toxlet.2020.06.020. Epub 2020 Jun 21.
Non-alcoholic fatty liver disease (NAFLD) can be typically classified into two subgroups: non-alcoholic fatty liver and non-alcoholic steatohepatitis. Mouse models of NAFLD are useful tools for understanding the pathogenesis and progression of NAFLD and for developing drugs for its treatment. Here, we investigated the time-dependent changes in serum lipids and biochemical markers of hepatic function, hepatic inflammation, and fibrosis in mice fed a normal diet (ND) or a NAFLD diet (choline deficient, L-amino acid-defined, high-fat diet; CDAHFD) for 12 weeks. CDAHFD-fed mice showed significantly reduced serum levels of total cholesterol, triglyceride, and high-density lipoprotein cholesterol throughout the treatment period compared with ND-fed mice. The changes in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and total bilirubin showed an inverse U-shaped curve in the CDAHFD-fed mice. The serum alkaline phosphatase levels decreased in both ND- and CDAHFD-fed mice in a time-dependent manner. Furthermore, CDAHFD-fed mice showed a significant increase in the number of inflammatory foci and hepatic fibrosis at 6-12 weeks, although inflammatory foci and hepatic fibrogenesis were observable at relatively early stages as well (1-4 weeks). In conclusion, the long-term profile of serological biomarkers, hepatic inflammation, and fibrosis in CDAHFD-fed mice identified in this study may provide a better understanding of NAFLD pathogenesis.
非酒精性脂肪性肝病（NAFLD）通常可分为两个亚组：非酒精性脂肪肝和非酒精性脂肪性肝炎。NAFLD小鼠模型是理解NAFLD发病机制和进展以及开发其治疗药物的有用工具。在此，我们研究了喂食正常饮食（ND）或NAFLD饮食（胆碱缺乏、L-氨基酸定义的高脂饮食；CDAHFD）12周的小鼠血清脂质以及肝功能、肝脏炎症和纤维化生化标志物的时间依赖性变化。与喂食ND的小鼠相比，喂食CDAHFD的小鼠在整个治疗期间血清总胆固醇、甘油三酯和高密度脂蛋白胆固醇水平显著降低。喂食CDAHFD的小鼠中，天冬氨酸转氨酶、丙氨酸转氨酶、乳酸脱氢酶和总胆红素的变化呈倒U形曲线。喂食ND和CDAHFD的小鼠血清碱性磷酸酶水平均呈时间依赖性下降。此外，尽管在相对早期阶段（1-4周）也可观察到炎症灶和肝纤维化，但喂食CDAHFD的小鼠在6-12周时炎症灶数量和肝纤维化显著增加。总之，本研究中确定的喂食CDAHFD小鼠血清生物标志物、肝脏炎症和纤维化的长期概况可能有助于更好地理解NAFLD的发病机制。
