基于血清代谢组学分析热习服相关代谢产物及通路特征

Analysis of heat acclimatization related metabolites and pathway characteristics based on serum metabonomics

目的分析热习服与未习服人员血清中小分子代谢物的差异,揭示人体热习服相关血清小分子代谢物特征。方法选择70例由温到热跨域作业的健康男性为研究对象,以跨域后暴露于自然高温高湿环境作业或人工空调舒适环境作业为标准,分为热习服组(n=40)和未习服组(n=30)。收集所有研究对象跨域后2个月时的清晨空腹血液样本,经标准处理后采用液相色谱-串联质谱法进行代谢组学检测,用Progenesis QI软件和R 1.6.2软件ropls包筛选两组人员的差异小分子代谢物,对差异小分子代谢物进行京都基因与基因组百科全书(KEGG)通路富集分析。结果两组研究对象年龄和BMI差异无统计学意义(均P>0.05)。血清代谢组学检测共发现小分子代谢物1320个,正交偏最小二乘判别分析结果显示,热习服组和未习服组样本表现出良好的组间区分和组内聚集。两组血清样本间浓度差异在1.5倍(P<0.05)以上的小分子代谢物有89个,其中57个在热习服组升高、32个在热习服组降低;KEGG通路富集分析显示,差异小分子代谢物主要富集于氨基酸代谢和甘油磷脂代谢等13条代谢通路,涉及色氨酸、甘氨酸、丝氨酸、苏氨酸、精氨酸和脯氨酸等通路。结论热环境暴露下的热习服训练改变了人体血清小分子代谢物的组学特征,表现为氨基酸代谢水平增强,其可能与热耐力的维护有关。

Objective To compare the serum small molecule metabolites between heat acclimatization and heat non-acclimatization subjects,and reveal the characteristics of serum small molecule metabolites related to human heat acclimatization.Methods Seventy subjects involved in a cold-to-heat region transferring were enrolled in this study.According to the exposure to a high wet-heat natural environment or a comfortable air-condition artificial environment,the subjects were divided into heat acclimatization group(n=40)and heat non-acclimatization group(n=30).Early morning fasting blood samples from the subjects were collected 2 months after region transferring.After standard processing,liquid chromatography tandem mass spectrometry was used for metabolomic detection,and Progenesis QI software and ropls tool of R 1.6.2 software were employed to identify the differential small molecule metabolites of the 2 groups,and the pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)was carried out for the differential small molecule metabolites.Results There were no significant differences in age or body mass index between the 2 groups(both P>0.05).A total of 1320 small molecule metabolites were detected by serum metabolomics.Orthogonal partial least squares-discriminant analysis showed that the samples of heat acclimatization group and heat non-acclimatization group had a good discrimination between groups and a good aggregation within groups.There were 89 small molecule metabolites with a concentration difference of more than 1.5 times(P<0.05)between the 2 groups,with 57 being increased and 32 being decreased in the heat acclimatization group.KEGG pathway enrichment analysis showed that the differential small molecule metabolites were mainly enriched in 13 metabolic pathways,including amino acid metabolism and glycerophospholipid metabolism,involving tryptophan,glycine,serine,threonine,arginine,and proline.Conclusion Heat acclimatization training under heat exposure can change the omics characteristics of small molecule metabolites in human serum,mainly enhancing amino acid metabolism involved in heat tolerance.