Rapid lipidomics analysis for sepsis-induced liver injury in rats and insights into lipid metabolic pathways using ultra-performance liquid chromatography/mass spectrometry.

Lipidomics has been applied in the identification and quantification of molecular lipids within an organism, and to provide insights into mechanisms in clinical medicine. Sepsis is a major systemic inflammatory syndrome and the liver here is a potential target organ for dysfunctional response. However, the study of alterations in global lipid profiles associated with sepsis-induced liver injury is still limited. In this work, we set out to determine alterations of lipidomics profiles in a rat model of sepsis-induced liver injury using an untargeted lipidomics strategy. Liquid chromatography coupled with mass spectrometry in conjunction with multivariate data analysis and pathway analysis were used to acquire a global lipid metabolite profile. Meanwhile, biochemistry index and histopathological examinations of the liver were performed to obtain auxiliary measurements for determining the pathological changes associated with sepsis-induced liver injury. Eleven lipid metabolites and two metabolic pathways were discovered and associated with sepsis-induced liver injury. The results indicated that various biomarkers and pathways may provide evidence for and insight into lipid profile alterations associated with sepsis-induced liver injury, and hence pointed to potential strategic targets for clinical diagnosis and therapy in the future.

High-throughput metabolic profiling, combined with chemometrics and bioinformatic analysis reveals functional alterations in myocardial dysfunction.

High-throughput metabolic profiling technology has been used for biomarker discovery and to reveal underlying metabolic mechanisms. Sepsis-induced myocardial dysfunction (SMD) is a common complication in sepsis patients, and severely affects their quality of life. However, the pathogenesis of SMD is currently unclear, and there has been inadequate basic research. In this study, metabolic profiling was explored by liquid chromatography/mass spectrometry (LC/MS) combined with chemometrics and bioinformatic analysis. The global metabolome data were analyzed using chemometrics analysis including principal component analysis and partial least squares discriminant analysis for significant metabolites. Variable importance for projection values obtained utilizing a pattern recognition method were used to identify potential biomarkers. The differential metabolites were putatively identified using the metabolome database and bioinformatics analysis was conducted via Ingenuity Pathway Analysis (IPA) to predict the likely functional alterations. In total, 21 differential metabolites were found in SMD and these were involved in phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, glycine, serine and threonine metabolism, and so on. The analysis revealed that the metabolites were strongly related to molecular transport, and small molecule biochemistry metabolic pathways. The present study indicates that high-throughput metabolic profiling, combined with chemometrics and a bioinformatic platform, can reveal the likely functional alterations in disease and could provide more precise and credible information in the basic research of disease pathogenesis.