Altered Metabolic Profile of Triglyceride-Rich Lipoproteins in Gut-Lymph of Rodent Models of Sepsis and Gut Ischemia-Reperfusion Injury.

Abstract

BACKGROUND:Triglyceride-rich lipoproteins are important in dietary lipid absorption and subsequent energy distribution in the body. Their importance in the gut-lymph may have been overlooked in sepsis, the most common cause of critical illness, and in gut ischemia-reperfusion injury, a common feature of many critical illnesses. AIMS:We aimed to undertake an exploratory study of triglyceride-rich lipoprotein fractions in gut-lymph using untargeted metabolic profiling to identify altered metabolites in sepsis or gut ischemia-reperfusion. METHODS:The gut-lymph was collected from rodent sham, sepsis, and gut ischemia-reperfusion models. The triglyceride-rich lipoprotein-enriched fractions isolated from the gut-lymph were subjected to a dual metabolomics analysis approach: non-polar metabolite analysis by ultra-high performance liquid chromatography-mass spectrometry and polar metabolite analysis by gas chromatography-mass spectrometry. RESULTS:The metabolite analysis of gut-lymph triglyceride-rich lipoprotein fractions revealed a significant increase (FDR-adjusted P value < 0.05) in myo-inositol in the sepsis group and monoacylglycerols [(18:1) and (18:2)] in gut ischemia-reperfusion. There were no significantly increased specific metabolites in the lipoprotein-enriched fractions of both sepsis and gut ischemia-reperfusion. In contrast, there was a widespread decrease in multiple lipid species in sepsis (35 out of 190; adjusted P < 0.05), but not in the gut ischemia-reperfusion. CONCLUSIONS:Increased levels of myo-inositol and monoacylglycerols, and decreased multiple lipid species in the gut-lymph triglyceride-rich lipoprotein fraction could be candidates for new biomarkers and/or involved in the progression of sepsis and gut ischemia-reperfusion pathobiology.