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Metabolomics reveals increased isoleukotoxin diol (12,13-DHOME) in human plasma after acute Intralipid infusion

Citation

Edwards, LM and Lawler, NG and Nikolic, SB and Peters, JM and Horne, J and Wilson, R and Davies, NW and Sharman, JE, Metabolomics reveals increased isoleukotoxin diol (12,13-DHOME) in human plasma after acute Intralipid infusion, Journal of Lipid Research, 53, (9) pp. 1979-1986. ISSN 0022-2275 (2012) [Refereed Article]


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Copyright Statement

Copyright 2012 American Society for Biochemistry and Molecular Biology

DOI: doi:10.1194/jlr.P027706

Abstract

Intralipid is a fat emulsion that is regularly infused into humans and animals. Despite its routine use, Intralipid infusion can cause serious adverse reactions, including immunosuppression. Intralipid is a complex mix of proteins, lipids, and other small molecules, and the effect of its infusion on the human plasma metabolome is unknown. We hypothesized that untargeted metabolomics of human plasma after an Intralipid infusion would reveal novel insights into its effects. We infused Intralipid and saline into 10 healthy men in a double-blind, placebo-controlled experiment and used GC/MS, LC/MS, and NMR to profile the small-molecule composition of their plasma before and after infusion. Multivariate statistical analysis of the 40 resulting plasma samples revealed that after Intralipid infusion, a less-well-characterized pathway of linoleic acid metabolism had resulted in the appearance of (9Z)-12,13-dihydroxyoctadec-9-enoic acid (12,13-DHOME, P < 10-3), a leukotoxin that has powerful physiological effects and is known to inhibit the neutrophil respiratory burst. Intralipid infusion caused increased plasma 12,13-DHOME. Given that 12,13-DHOME is known to directly affect neutrophil function, we conclude that untargeted metabolomics may have revealed a hitherto-unknown mechanism of intralipid-induced immunosuppression.

Item Details

Item Type:Refereed Article
Keywords:fatty acid/metabolism, mass spectrometry, triglycerides, (9Z)-12,13-dihydroxyoctadec-9-enoic acid
Research Division:Medical and Health Sciences
Research Group:Medical Biochemistry and Metabolomics
Research Field:Medical Biochemistry and Metabolomics not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cardiovascular System and Diseases
Author:Lawler, NG (Mr Nathan Lawler)
Author:Nikolic, SB (Mrs Sonja Nikolic)
Author:Peters, JM (Mr James Peters)
Author:Horne, J (Dr James Horne)
Author:Wilson, R (Dr Richard Wilson)
Author:Davies, NW (Associate Professor Noel Davies)
Author:Sharman, JE (Professor James Sharman)
ID Code:80113
Year Published:2012
Web of Science® Times Cited:17
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-10-23
Last Modified:2017-11-06
Downloads:0

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