Graduate Institute of Veterinary Pathobiology, National Chung Hsing University, Taichung, 402, Taiwan.
Division of Animal Industry, Animal Technology Laboratories, Agricultural Technology Research Institute, Miaoli, 350, Taiwan.
J Nutr Biochem. 2020 May;79:108362. doi: 10.1016/j.jnutbio.2020.108362. Epub 2020 Feb 24.
Diet-induced obesity is the most widely used animal model for studying nonalcoholic fatty liver disease (NAFLD). However, the physiological effects of a high-fat diet (HFD) are inconsistent between different studies. To elucidate this mystery, mice raised with conventional (CONV), specific pathogen-free (SPF) and gentamicin (G) treatments and fed with standard diet (STD) or HFD were analyzed in terms of their physiology, gut microbiota composition, hepatic steatosis and inflammation. Serum biochemistry showed increased levels of cholesterol and aspartate aminotransferase in the G-STD and CONV-HFD groups, respectively. The CONV-HFD group exhibited more inflammatory foci compared to the SPF-HFD and G-HFD groups. Furthermore, immunohistochemistry staining revealed the infiltration of Kupffer cells in the liver, consistent with increased mRNA levels of MCP-1, CD36 and TLR4. Principal coordinate analysis and the cladogram of LEfSe showed that the distinguished clusters of gut microbiota were dependent on housing conditions. The Rikenellaceae, F16 and Desulfovibrionaceae were strongly correlated with hepatic inflammation. Otherwise, higher NAFLD activity score correlated with altered relative abundances of Bacteroidetes and Firmicutes. In conclusion, gut microbiota varying with housing condition may be pivotal for the host response to HFD.
饮食诱导肥胖是研究非酒精性脂肪性肝病（NAFLD）最常用的动物模型。然而，高脂肪饮食（HFD）的生理效应在不同的研究中并不一致。为了阐明这一奥秘，本研究分析了采用常规（CONV）、无特定病原体（SPF）和庆大霉素（G）处理并分别给予标准饮食（STD）或 HFD 的小鼠的生理学、肠道微生物群落组成、肝脂肪变性和炎症情况。血清生化分析显示，G-STD 和 CONV-HFD 组的胆固醇和天冬氨酸转氨酶水平分别升高。与 SPF-HFD 和 G-HFD 组相比，CONV-HFD 组表现出更多的炎症灶。此外，免疫组织化学染色显示肝脏中库普弗细胞浸润，与 MCP-1、CD36 和 TLR4 的 mRNA 水平升高一致。主坐标分析和 LEfSe 的系统发育树显示，肠道微生物群落的显著聚类依赖于饲养条件。Rikenellaceae、F16 和脱硫弧菌科与肝炎症强烈相关。相反，较高的 NAFLD 活动评分与厚壁菌门和拟杆菌门相对丰度的改变相关。总之，随饲养条件变化的肠道微生物群可能是宿主对 HFD 反应的关键。
