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Digestive Diseases and Sciences

, Volume 63, Issue 12, pp 3317–3328 | Cite as

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

  • Jiwon HongEmail author
  • Shorena Nachkebia
  • Soe Min Tun
  • Amorita Petzer
  • John A. Windsor
  • Anthony J. Hickey
  • Anthony R. Phillips
Original Article

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.

Keywords

Metabolomics Lipoproteins Lymph Gut Critical illness 

Abbreviations

APO

Apolipoprotein

DG

Diacylglycerol

GC–MS

Gas chromatography–mass spectrometry

IR

Ischemia-reperfusion

LPC

Lysophosphatidylcholine

LPE

Lysophosphatidylethanolamine

MG

Monoacylglycerol

MAP

Mean arterial pressure

MODS

Multiple organ dysfunction syndrome

PC

Phosphocholine

PE

Phosphoethanolamine

PS

Phosphoserine

QC

Quality control

TG

Triglyceride

TRL

Triglyceride-rich lipoprotein

UHPLC–MS

Ultra-high performance liquid chromatography–mass spectrometry

VLDL

Very low-density lipoprotein

Notes

Acknowledgments

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.

Author’s contributions

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.

Funding

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.

Ethical approval

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.

Supplementary material

10620_2018_5270_MOESM1_ESM.xlsx (155 kb)
Supplementary material 1 (XLSX 155 kb)
10620_2018_5270_MOESM2_ESM.docx (932 kb)
Supplementary material 2 (DOCX 931 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Biological SciencesUniversity of AucklandAucklandNew Zealand
  2. 2.Department of SurgeryUniversity of AucklandAucklandNew Zealand

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