Altered Metabolic Profile of Triglyceride-Rich Lipoproteins in Gut-Lymph of Rodent Models of Sepsis and Gut Ischemia-Reperfusion Injury
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.
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.
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.
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.
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.
KeywordsMetabolomics Lipoproteins Lymph Gut Critical illness
Gas chromatography–mass spectrometry
Mean arterial pressure
Multiple organ dysfunction syndrome
Ultra-high performance liquid chromatography–mass spectrometry
Very low-density lipoprotein
We wish to thank C Keven of the Liggins Institute, University of Auckland, for the biochemical analyte measurements; S Church and P Begley from the Centre for Advanced Discovery and Experimental Therapeutics, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health at the University of Manchester, UK (supported by the NIHR Manchester Biomedical Research Centre), for their technical assistance with the metabolomic analyses.
JH, ARP, AJH, and JAW designed the studies. SN, SMT, and AP performed animal surgery. JH interpreted the data and wrote the manuscript, and ARP, AJH, and JAW edited the manuscript. All authors approved the manuscript.
This work was supported by the Early Careers Academic Grants, Association of Commonwealth Universities; Maurice and Phyllis Paykel Trust; Performance-Based Research Fund, University of Auckland; Auckland Medical Research Foundation; Faculty Research Development Fund, University of Auckland; and Health Research Council of New Zealand.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
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