与肥胖关联环境化学物质的比较基因组学分析

Comparative genomics analysis on association between environmental chemicals and obesity

目的越来越多的证据表明,环境化学物质与肥胖间存在关联。本次研究初步探讨环境化学物质引起肥胖的可能分子生物学机制。方法借助比较毒理基因组学数据库(Comparative Toxicogenomics Database,CTD),获取与肥胖关联的环境化学物质及其相互作用的基因,选取环境化学物与肥胖高度相关的基因进行基因本体分析和KEGG信号通路等基因富集分析。结果与肥胖相关的环境化学物质共1 844种,其中264种药物、112种环境污染物,12类饮食成分,9类农药及其他物质,共筛查出158个与肥胖高度相关的人类基因。基因本体学分析表明,环境化学物质与肥胖主要通过葡萄糖代谢、老化、药物应答、摄食行为、胰岛素应答等生物学进程相关;与线粒体、细胞间隙、分泌颗粒内腔、细胞外来体、胞外区、线粒体基质等细胞组分相关;与药物结合、RNA聚合酶II转录因子活性,配体活化序列特异性DNA结合、同种基因结合、酶结合、转录因子结合、类固醇激素受体活性、激素活性等分子功能相关。信号通路富集结果表明与脂肪细胞因子信号通路、脂类分解调节、AMPK信号通路、PPAR信号通路、非酒精性脂肪性肝病、胰岛素抵抗、丙酸代谢信号通路等信号通路有关。结论环境化学物质可能通过影响基因表达从而引起某些信号通路的改变等内在分子生物学机制与肥胖间产生关联,可能的因果关联尚需要进一步研究。

Objective Accumulating evidence suggests that there are associations between environmental chemicals and obesity in human.This study investigates the possible molecular mechanism of obesity caused by environmental chemicals. Methods The associated environmental chemicals and gene associated with obesity were obtained by Comparative Toxicogenomics Database.Then,the target gene associated with environmental chemicals and obesity were used to perform gene function enrichment analysis with gene ontology and KEGG pathway. Results Totally 1 884 environmental chemicals,including 264 drugs,112 environmental pollutants,12 diets,9 pesticides and other environmental chemicals were associated with obesity.A total of 158 human genes the most associated with obesity were screened.Genetic ontology analysis indicated that environmental chemicals played a biological role on obesity mainly through biological process of glucose metabolic process,aging,response to drug,feeding behavior,response to insulin,through cellular component of mitochondrion,extracellular space,secretory granule lumen,extracellular exosome,extracellular region,mitochondrial matrix,through molecular function of drug binding,RNA polymerase II transcription factor activity,ligand-activated sequence-specific DNA binding,identical protein binding,enzyme binding,transcription factor binding,steroid hormone receptor activity,hormone activity.The signaling pathway enrichment results showed that the environmental chemicals might influence obesityby adipocytokine signaling pathway,regulation of lipolysis in adipocytes,AMPK,PPAR,non-alcoholic fatty liver disease（NAFLD）,insulin resistance,propanoate metabolism. Conclusion Environmental chemicals might cause obesity by changing the expression of the genes involved in some signaling pathways.Further studies need for further test the possible causal association between environmental chemicals and obesity.