Non-targeted Lipomics Analysis of the Effects of Fumonisin B1 on the Lipid Metabolism in Immature Dendritic Cells
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摘要: 伏马菌素B1 (fumonisin B1, FB1)是一种具有免疫抑制作用的真菌毒素。本研究利用FB1处理未成熟树突状细胞(immature dendritic cells, imDCs),通过非靶向脂质组学分析FB1对imDCs脂质代谢的影响。运用超高效液相色谱串联四极杆静电场轨道阱质谱(UPLC-Q-Exactive Orbitrap-MS)技术采集质谱数据,通过主成分分析(principal component analysis, PCA)、偏最小二乘法判别分析(partial least-squares discrimination analysis, PLS-DA)和正交偏最小二乘法判别分析(orthogonal partial least-squares discrimination analysis, OPLS-DA)进行多维统计分析,比较FB1处理组和对照组之间脂质代谢谱的差异,并以OPLS-DA模型的变量权重值(variable importance for the projection, VIP)>1和P<0.05为标准筛选差异脂质分子。脂质组学分析结果显示,从imDCs中共检测到36个脂质亚类,1 845个脂质分子。从FB1处理的imDCs中筛选出30个显著性差异脂质分子,其中神经酰胺(ceramide, Cer)、磷酸神经酰胺(ceramide phosphate, CerP)、单半乳糖甘油二酯(monogalactosyldiacylglycerol, MGDG)、磷脂酰胆碱(phosphatidylcholine, PC)、鞘氨醇(sphingosine, So)、磷脂酰丝氨酸(phosphatidylserine, PS)和鞘磷脂(sphingomyelin, SM)等亚类的含量显著下降(VIP>1,P<0.05),而甘油二酯(diacylglycerol, DG)和磷脂酰肌醇(phosphatidylinositol, PI)的含量显著升高(VIP>1,P<0.05)。研究结果说明FB1可能通过干扰imDCs的正常脂质代谢来发挥其免疫抑制作用。Abstract: Fumonisin B1(FB1) is a mycotoxin with immunosuppressive effect. In this study, FB1 was used to treat immature dendritic cells(imDCs), and non-targeted lipidomics analysis was deployed to analyze the effects of FB1 on the lipid metabolism in imDCs. Mass spectrum data were collected by UPLC-Q-Exactive Orbitrap-MS technology and multivariate statistical analyses were carried out by the principal component analysis(PCA), partial least squares discrimination analysis(PLS-DA) and orthogonal partial least-squares discriminant analysis(OPLS-DA). The differences of lipid metabolism profiles between FB1-treated group and control group were compared, and the differential lipid molecules were screened with the criterion of variable importance for the projection(VIP)>1 in the OPLS-DA model and P<0.05. The results showed that a total of 36 lipid subclasses and 1 845 lipid molecules in imDCs were detected by the lipidomics analysis. After treatment with FB1, 30 lipid molecules in imDCs with significant differences were screened. Among them, the contents of some lipid subclasses, such as ceramide(Cer), ceramide phosphate(CerP), monogalactosyldiacylglycerol(MGDG), phosphatidylcholine(PC), sphingosine(So), phosphatidylserine(PS) and sphingomyelin(SM) decreased significantly(VIP>1, P<0.05), while the levels of diacylglycerol(DG) and phosphatidylinositol(PI) increased significantly(VIP>1, P<0.05). The research results suggested that FB1 may exert immunosuppressive effect by interfering with the normal lipid metabolism in imDCs.
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Keywords:
- Fumonisin B1 /
- Dendritic cells /
- Lipomics /
- Lipid metabolite /
- Sphingolipid metabolism
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