A lipidomic study on extensive plasma lipids in bacterial peritonitis (cecal ligation and puncture, CLP)-induced sepsis in mice was done at 24 h post-CLP. The effects of administration of lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), compounds known to have beneficial effects in CLP...
A lipidomic study on extensive plasma lipids in bacterial peritonitis (cecal ligation and puncture, CLP)-induced sepsis in mice was done at 24 h post-CLP. The effects of administration of lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), compounds known to have beneficial effects in CLP, on the sepsis-induced plasma lipid changes were also examined. Among the 147 plasma lipid species from 13 lipid subgroups (fatty acid [FA], LPA, LPC, lysophosphatidylethanolamine [LPE], phosphatidic acid [PA], phosphatidylcholine [PC], phosphatidylethanolamine [PE], phosphatidylinositol [PI], monoacylglyceride [MG], diacylglyceride [DG], triacylglyceride [TG], sphingomyelin [SM], and ceramide [Cer]) analyzed in this study, 40 and 70 species were increased, and decreased, respectively, in the CLP mice. Treatments with LPC and LPA affected 14 species from 7 subgroups, and 25 species from 9 subgroups, respectively. These results could contribute to finding the much needed reliable biomarkers of sepsis.
A lipidomic study on extensive plasma lipids in bacterial peritonitis (cecal ligation and puncture, CLP)-induced sepsis in mice was done at 24 h post-CLP. The effects of administration of lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), compounds known to have beneficial effects in CLP, on the sepsis-induced plasma lipid changes were also examined. Among the 147 plasma lipid species from 13 lipid subgroups (fatty acid [FA], LPA, LPC, lysophosphatidylethanolamine [LPE], phosphatidic acid [PA], phosphatidylcholine [PC], phosphatidylethanolamine [PE], phosphatidylinositol [PI], monoacylglyceride [MG], diacylglyceride [DG], triacylglyceride [TG], sphingomyelin [SM], and ceramide [Cer]) analyzed in this study, 40 and 70 species were increased, and decreased, respectively, in the CLP mice. Treatments with LPC and LPA affected 14 species from 7 subgroups, and 25 species from 9 subgroups, respectively. These results could contribute to finding the much needed reliable biomarkers of sepsis.
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제안 방법
PLS-DA score plots according to CLP and LPC/LPA treatment. Pattern analysis based on target analysis data was performed using the PLS-DA model and Mann-Whitney U-test between the sham group and sepsis groups (A), CLP and LPC/LPA treatment groups (B), and each lysophospholipid (C, D).
To investigate the significant differences according to lipid classes and acyl chain components of lipid species, we performed the statistical analysis (p1). Among lipid classes, sphingolipids (SM and Cer) and glycerolipids (MG, DG, and TG) showed remarkable difference between sham and CLP mice (Fig.
대상 데이터
Metabolites were identified using the LipidMap (www.lipidmaps.org) and Human Metabolome databases (www.hmdb.ca) and confirmed using standard samples (Avanti Polar Lipids) based on retention time, mass spectra, and precursor ion of MS/MS spectra.
데이터처리
To investigate the effect of LPC or LPA on lipid metabolites in CLP, we performed the pattern analysis using the PLS-DA model and Mann–Whitney U-test.
이론/모형
Cross-validation with seven crossvalidation groups was used throughout the analysis to determine the number of principal components. A partial least-squares discriminant analysis (PLS-DA) was used as classification methods to model the discrimination by visualizing the score plot.
성능/효과
Among the 147 plasma lipid species analyzed in this study, levels of 110 species were changed in the CLP; 40 species were increased, and 70 species were decreased. LPC and LPA treatment affected 14 lipid species of 7 subgroups, and 25 lipid species of 9 subgroups, respectively.
The glycerolipids levels were dramatically reduced about 90% in CLP group compared with sham group. By the LPA treatment in CLP mice, the species of MG and DG showed significantly increased levels; particularly, the levels of MG 16:0 and 18:0 and DG 36:0 were elevated by 94%, 171%, and 47% compared with CLP group, respectively. By the LPC treatment in CLP mice, the species of TG showed significantly decreased levels; particularly, the levels of TG 48:1 and 48:2 were decreased by 88% and 80% compared with CLP group, respectively.
By the LPA treatment in CLP mice, the species of MG and DG showed significantly increased levels; particularly, the levels of MG 16:0 and 18:0 and DG 36:0 were elevated by 94%, 171%, and 47% compared with CLP group, respectively. By the LPC treatment in CLP mice, the species of TG showed significantly decreased levels; particularly, the levels of TG 48:1 and 48:2 were decreased by 88% and 80% compared with CLP group, respectively.
Phospholipids (PA, PC, PE, and PI) showed diverse changes in CLP; PAs and PEs mostly increased, while PCs either increased or decreased depending on the PC species, and all the PIs decreased (Fig. 8). Lysophospholipids (LPA, LPC, and LPE) also revealed diverse changes in CLP; LPAs showed varied changes, while LPCs and LPEs more likely decreased in CLP (Fig.
The levels of LPA 20:0 and 22:0, LPC 18:0, 18:2, 20:2, 22:1, and 22:5, and PC 36:0 were significantly increased in LPC or LPA treatment groups when compared with the non-treatment group (CLP group), whereas the levels of PC 30:0 and 30:1 and PE 34:1 were significantly decreased in LPC or LPA treatment groups.
The species of SM and Cer had significantly higher levels in CLP mice than sham mice, and particularly SM d36:1 and d38:1 had remarkably high levels in CLP mice (>400%). The species of MG, DG, and TG showed significantly lower levels in CLP mice than sham mice, except DG containing carbon number 38 and double bond number 4 and 5 and TG containing carbon number 56 and 58 and double bond number more than 6 (TG 56:7, 56:8, 58:8, 58:9, and 58:10).
The species of SM and Cer had significantly higher levels in CLP mice than sham mice, and particularly SM d36:1 and d38:1 had remarkably high levels in CLP mice (>400%).
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