Comprehensive Evaluation of Lipopolysaccharide-Induced Changes in Rats Based on Metabolomics

PURPOSE: Substantial evidence indicates that lipopolysaccharide (LPS) exposure can lead to systemic inflammatory response syndrome (SIRS) and multiple organ failure. Previous metabolomic studies have mainly focused on LPS-induced depression or hepatic and renal effects. However, no comprehensive metabolomics-based analysis of the serum, liver, kidney, hippocampus, and heart following exposure to LPS has been undertaken to date. MATERIAL AND METHODS: Male Sprague–Dawley rats were randomly allocated to a control and a LPS-treated group (n=8). LPS for 2 weeks (0.5 mg/kg every other day) was given via intraperitoneal injection. Gas chromatography–mass spectrometry (GC–MS) was used for metabolite determination, while multivariate statistical analysis was performed to identify differentially expressed metabolites between the two groups. RESULTS: Our study revealed that 24, 13, 12, 7, and 12 metabolites were differentially expressed between the LPS treatment group and the control group in the serum, liver, kidney, hippocampus, and heart, respectively. We further identified that these metabolic changes were mainly involved with aminoacyl-tRNA biosynthesis; glutathione metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; arginine biosynthesis; bile acid biosynthesis; and glycerolipid metabolism. CONCLUSION: We have systematically elucidated the metabolic changes underlying LPS-induced SIRS, thereby providing insight into the mechanisms associated with these alterations.