夜间光暴露小鼠肝脏非靶向代谢组学研究

Effect of light at night on liver metabolism in mice by untargeted metabolomics

目的观察夜间光暴露下小鼠肝脏代谢谱变化。方法选择健康雄性C57BL/6J小鼠随机分为夜间光暴露组和对照组,每组8只。夜间光暴露组光照/黑暗周期为24 h/0 h,对照组为12 h/12 h,连续10 d。采用高效液相色谱-串联质谱分析法检测两组小鼠的肝脏代谢物,采用主成分分析和正交偏最小二乘法判别分析等方法评价小鼠夜间光暴露建模效果,利用KEGG数据库分析两组小鼠代谢物变化。结果相较于对照组,夜间光暴露组小鼠共检出9种主要差异代谢物,其中甘氨酸-甜菜碱、谷胱甘肽、酪氨酸、甜菜碱、赖氨酸、次黄嘌呤、组氨酸和蛋氨酸含量降低,甘露糖-6-磷酸含量升高。代谢通路权重分析显示,夜间光暴露对小鼠肝脏物质代谢通路影响较大的主要有苯丙氨酸-酪氨酸-色氨酸代谢、酪氨酸代谢、果糖和甘露糖代谢、半胱氨酸和蛋氨酸代谢、组氨酸代谢。结论夜间光暴露小鼠肝脏关键差异代谢物为酪氨酸、蛋氨酸、组氨酸和甘露糖-6-磷酸等,可能影响氨基酸和糖代谢通路。

Objective To observe the changes of liver metabolism in mice exposed to artificial light at night.Methods Healthy male C57BL/6J mice were randomly divided into the light at night group and the control group,with 8 mice in each group.The daily light/dark cycle was 12/12 hours in the control group,and 24/0 hours in the light at night group for 10 consecutive days.The hepatic metabolite profiles of the two groups of mice were detected by high performance liquid chromatography tandem mass spectrometry.The modelling was assessed by combining principal component analysis(PCA)and orthogonal partial least squares-discriminant analysis(OPLS-DA),The changes of metabolites in the two groups were compared through KEGG database.Results Compared with the control group,9 different metabolites were detected in the light at night group,among which the down-regulated metabolites were glycine-betaine,glutathione,tyrosine,betaine,lysine,hypoxanthine,histidine and methionine,and the up-regulated ones were mannose-6-phosphate.The weight analysis of the metabolic pathways showed that the major influences on liver of light at night group were phenylalanine-tyrosine-tryptophan metabolism,tyrosine metabolism,fructose and mannose metabolism,cysteine and methionine metabolism and histidine metabolism.Conclusion The metabolism of various amino acids and sugars in light at night mice is disturbed,and the key differential metabolites are tyrosine,methionine,histidine and mannose-6-phosphate.