转录组学分析月桂酸单甘油酯对HepG2细胞脂代谢的调节作用  

Regulation Effect Analysis of Glycerol Monolaurate on Lipid Metabolism of HepG2 Based on Transcriptomics

作　　者：林萌慧 刘畅 黄佳敏 冯凤琴[2] Le Thanh Ninh 蔡海莺[1,2,3] Lin Menghui;Liu Chang;Huang Jiamin;Feng Fengqin;Le Thanh Ninh;Cai Haiying(School of Biological and Chemical Engineering,Zhejiang University of Science and Technology,Hangzhou 310023;College of Biosystems Engineering and Food Science,Zhejiang University,Hangzhou 310058;Department of Food Science and Technology,National University of Singapore,Singapore 119077)

机构地区：[1]浙江科技学院生物与化学工程学院,杭州3100232 [2]浙江大学生物系统工程与食品科学学院,杭州3100583 [3]新加坡国立大学食品科学与技术系,新加坡119077

出　　处：《中国食品学报》2024年第8期101-111,共11页Journal of Chinese Institute Of Food Science and Technology

基　　金：国家自然科学基金面上项目(31972079,32172214);浙江省自然科学基金一般项目(LQ19E030001,LY18C200006);国家级大学生创新创业训练计划项目(202211057021)。

摘　　要：为阐明月桂酸单甘油酯(GML)调节脂代谢的具体靶点和信号通路,本研究通过GML处理油酸诱导的肝脏肿瘤细胞HepG2高脂模型,结合生物信息学预测和细胞转录组测序分析GML对肝细胞脂代谢的调节作用及其潜在靶点和机制。生物信息学分析显示:通过GML潜在靶点的GO和KEGG富集分析,分别获得信号通路519个和144条(P<0.05)。分子对接验证GML可能通过调节ALB、AKT1、EGFR等核心靶点蛋白实现其对脂代谢的调控。细胞试验结果显示:经GML干预的细胞组与高脂对照组相比,脂质积累水平有一定改善。转录组分析共筛选出2879个差异表达基因,上调和下调分别为1363个和1516个。由KEGG信号通路富集分析可知,低氧诱导因子(HIF-1α)通路和脂肪酸氧化分解代谢通路基因富集较显著,通路中重要蛋白CPT1B、FABP1等基因转录水平表达处理组比高脂组分别上升1.79倍和2.81倍,且HIF-1α调控下游主要基因表达显著上升,表明GML干预以HIF-1α通路介导改善高脂细胞氧化应激,并通过脂肪酸分解途径改善高脂细胞模型的脂代谢紊乱。本研究为探索功能性油脂成分改善高脂膳食脂代谢紊乱的作用和机制提供一定的理论参考。In this study,to illustrate the specific regulation targets and pathways of glycerol monolaurate(GML)on lipid metabolism,GML was used to treat hyperlipidemia model of liver tumor cells HepG2 induced by oleic acid,and explore the regulation effects of GML on lipid metabolism of liver cells and its potential targets and mechanisms based on bioinformatics prediction and transcriptome sequencing analysis.Bioinformatics analysis showed that the GO and KEGG enrichment analysis of potential GML targets obtained 519 and 144 signal pathways(P<0.05),respectively.Molecular docking supported that GML might regulate lipid metabolism through regulating ALB,AKT1,EGFR and other core target proteins.The results of cell experiment showed that the level of lipid accumulation in the cell group treated with GML was improved compared with the high-fat control group.A total of 2879 differentially expressed genes were screened by transcriptome analysis,with 1363 up-regulated and 1516 down-regulated genes,respectively.According to the enrichment analysis of KEGG signal pathway,HIF-1αpathway and fatty acid oxidative catabolism pathway were significantly enriched.The gene transcription expression levels of important proteins CPT1B,FABP1 in the pathway were up-regulated to 1.79 times and 2.81 times in the GML treatment group compared with those in the high-fat group,respectively,and the expression levels of main downstream regulation genes of HIF-1αwere significantly increased(P<0.05),indicating that GML intervention improved the oxidative stress of high-fat cells through regulation of HIF-1αpathway,and improved the lipid metabolism disorder in high-fat cells mediated by fatty acid degradation pathway.This study provides a theoretical reference for the research on the regulation and mechanisms of functional lipid components in improving lipid metabolism disorder induced by high-fat diet.

关 键 词：月桂酸单甘油酯 脂肪酸氧化 脂代谢 分子对接 低氧诱导因子1Α 

分 类 号：TS221[轻工技术与工程—粮食、油脂及植物蛋白工程]