基于气相色谱-质谱的脂肪萎缩小鼠血浆代谢组学研究

Metabolite in Plasma of aP2-nSREBP-1c Mice with Lipoatrophy Using GC-MS Technology

目的:脂肪萎缩是引起糖脂代谢紊乱的重要因素之一。通过气相色谱-质谱联用(GC-MS)技术分析aP2-nSREBP-1c脂肪萎缩小鼠血浆代谢谱的变化,研究与其密切相关的差异代谢物与代谢通路,探讨其生物学基础。方法:应用GC-MS技术对6只同窝野生型小鼠和6只转基因小鼠血浆样品进行检测,对检测结果进行多元统计分析,筛选出显著差异的代谢物,借助MetaboAnalyst分析代谢通路。结果:与野生型(wild-type,WT)小鼠比较,转基因(transgenic,TG)小鼠血浆中乳酸、L-缬氨酸、3-羟基丁酸、尿素、d-半乳糖、D-阿洛糖、硬脂酸、棕榈酸、肌醇、油酸、11-十八碳烯酸含量增加。代谢通路富集分析发现3条脂肪萎缩相关通路。结论:通过对aP2-nSREBP-1c小鼠血浆代谢组学分析,发现缬氨酸、亮氨酸和异亮氨酸的生物合成,丙酮酸代谢,磷酸肌醇代谢途径与脂肪萎缩相关,为阐明糖脂代谢性疾病的发病机制提供了代谢组学依据。

Objective:To analyze the changes in plasma metabolism using gas chromatography-mass spectrometry (GC-MS) technology of aP2-nSREBP-1c mice with lipoatrophy.Study the differential metabolites and metabolic pathways that are closely related to lipoatrophic and explore its molecular mechanisms.Methods:Plasma samples of 6 wild-type mice in the in the control group and 6 transgene-type mice in the model group were detected using GC-MS.The result was analyzed by using multivariate statistical analysis,the metabolites were screened out which have significant difference.Results:Compared with the control group (wild-type,WT),the plasma levels of D-(-)-Lactic acid,L-Valine,(R)-3-Hydroxybutyric acid,Urea,d-Galactose,D-Allose,Stearic acid,Palmitic acid,Myo-Inositol,Oleic acid,11-Octadecenoic acid in the model group (transgene-type,TG) increased.Pathway enrichment analysis displayed that these metabolites were mainly involved in 3 metabolic pathways which were closely related to lipoatrophy.Conclusion:Through plasma metabonomics analysis of aP2-nSREBP-1c rats,metabolic information highly associate with lipoatrophy.The finding is helpful to provide a basis for understanding the molecular mechanisms of the disease.