Zhai Ruina, Feng Lei, Zhang Yu, Liu Wei, Li Shengli, Hu Zhiyong
College of Animal Science, Xinjiang Agricultural University, Urumqi, China.
Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian, China.
Front Nutr. 2021 Sep 17;8:733197. doi: 10.3389/fnut.2021.733197. eCollection 2021.
Non-alcoholic fatty liver disease develops from simple steatosis to non-alcoholic steatohepatitis (NASH), which then potentially develops into liver cirrhosis. It is a serious threat to human health. Therefore, investigating the formation and development mechanism of non-alcoholic fatty liver disease (NAFLD) is of great significance. Herein, an early model of NAFLD was successfully established by feeding rats with a high-fat and choline-deficient diet. Liver tissue samples were obtained from rats in the fatty liver model group (NAFL) and normal diet control group (CON). Afterward, transcriptome and lipidomic analysis was performed. Transcriptome results revealed that 178 differentially expressed genes were detected in NAFL and CON groups. Out of which, 105 genes were up-regulated, 73 genes were downregulated, and 8 pathways were significantly enriched. A total of 982 metabolites were detected in lipidomic analysis. Out of which 474 metabolites were significantly different, 273 were up-regulated, 201 were downregulated, and 7 pathways were significantly enriched. Based on the joint analysis, 3 common enrichment pathways were found, including cholesterol metabolism and fat digestion and absorption metabolic pathways. Overall, in the early stage of NAFLD, a small number of genetic changes caused a strong response to lipid components. The strongest reflection was glycerides and glycerophospholipids. A significant increase in fatty acid uptake accompanied by cholesterol metabolism is the most prominent metabolic feature of the liver in the early stage of NAFLD. In the early stage of fatty liver, the liver had shown the characteristics of NASH.
非酒精性脂肪性肝病从单纯性脂肪变性发展为非酒精性脂肪性肝炎（NASH），进而可能发展为肝硬化。它对人类健康构成严重威胁。因此，研究非酒精性脂肪性肝病（NAFLD）的形成和发展机制具有重要意义。在此，通过给大鼠喂食高脂肪和胆碱缺乏饮食成功建立了NAFLD早期模型。从脂肪肝模型组（NAFL）和正常饮食对照组（CON）的大鼠获取肝脏组织样本。随后，进行转录组和脂质组分析。转录组结果显示，在NAFL组和CON组中检测到178个差异表达基因。其中，105个基因上调，73个基因下调，8条通路显著富集。脂质组分析共检测到982种代谢物。其中474种代谢物有显著差异，273种上调，201种下调，7条通路显著富集。基于联合分析，发现3条共同富集通路，包括胆固醇代谢以及脂肪消化和吸收代谢通路。总体而言，在NAFLD早期，少数基因变化对脂质成分产生强烈反应。最强烈的反映是甘油酯和甘油磷脂。脂肪酸摄取显著增加并伴有胆固醇代谢是NAFLD早期肝脏最突出的代谢特征。在脂肪肝早期，肝脏已表现出NASH的特征。
