高脂饮食背景下小鼠肝脏脂质代谢重编程及免疫微环境重塑

Lipid metabolism reprogramming and immune microenvironment remodeling in mice liver under high-fat diet

目的探讨高脂饮食(high-fat diet,HFD)背景下的肝脏脂质代谢重编程及免疫微环境的改变。方法首先基于数据集GSE182668筛选出高脂饮食背景下的肝脏差异表达基因,通过基因本体论(gene ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)进行通路富集分析,使用String数据库对差异基因以互作评分>0.7分进行蛋白-蛋白互作(protein-protein interaction,PPI)网络构建,使用单样本基因集富集分析(single sample gene set enrichment analysis,ssGSEA)算法评估出各免疫细胞的浸润情况。结果高脂饮食背景下,过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)信号通路显著活化,脂质代谢相关基因ME1、CYP8B1、Bien、CYP4A1在HFD组中表达下调,而CYP7A1表达上调,肝脏免疫微环境发生显著改变。结论高脂饮食背景下,肝脏发生显著的脂质代谢重编程,并且伴随着肝脏免疫微环境的重塑。

Objective To investigate the changes of liver lipid metabolism reprogramming and immune microenvironment under high-fat diet(HFD).Methods Firstly,the differentially expressed genes in the liver under the background of high-fat diet were determined based on the data set GSE182668.Then,the pathway enrichment analysis was carried out by gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG),and the protein-protein interaction(PPI)network was constructed by String database with interaction score>0.7.Finally,the single sample gene set enrichment analysis(ssGSEA)algorithm was used to evaluate the infiltration of each immune cell.Results Under the background of highfat diet,peroxisome proliferator-activated receptor(PPAR)signaling pathway was significantly activated.The expression of lipid metabolism-related genes ME1,CYP8B1,Bien and CYP4A1 was down-regulated in the HFD group,while the expression of CYP7A1 was up-regulated,and the liver immune microenvironment was significantly changed.Conclusion Under the background of high-fat diet,the liver has obvious lipid metabolism reprogramming and is accompanied by the remodeling of liver immune microenvironment.