Summary of Study ST003137

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001950. The data can be accessed directly via it's Project DOI: 10.21228/M8NX50 This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003137
Study TitleLipid class-specific kinetics of plasma fatty acids, oxylipins, endocannabinoids, lysophospholipids and bile acids upon a lipopolysaccharide challenge of healthy humans and their modulation by anti-oxidative supplements (Part 1/2 - negative mode)
Study SummaryWhile molecular mechanisms of inflammatory processes are well characterized, the systemic responses of humans exposed to pathogen-associated molecular pattern with regard to fatty acid derivatives and other lipids have hardly been determined. Here, we present a dual stage controlled clinical intervention study with healthy individuals challenged with lipopolysaccharide. While in a first stage, plasma proteomics and lipidomics was applied to observe the kinetics of inflammatory modulators within eight hours, the effects of a placebocontrolled anti-oxidative intervention were determined in the second stage. Plasma proteome profiling demonstrated the early involvement of platelets detectable within two hours after lipopolysaccharide challenge, followed by the characteristic induction of liver-derived acute phase proteins and innate immune cell-derived alarmins. Untargeted lipidomics demonstrated the early release of fatty acids and taurocholic acid within two hours, followed by complex time courses of various oxylipins and the downregulation of numerous lysophospholipids and deoxycholic acid. Groups of molecules with similar kinetics during the time course analysis upon lipopolysaccharide challenge were observed to have common precursors or synthesizing enzymes. Dietary supplementation with antioxidants did not affect the kinetics of detectable proteins, but significantly downregulated the pro-inflammatory sphingosine-1-phosphate and increased the levels of oxylipins described to facilitate the resolution of inflammation, 20-HEPE and 22-HDoHE. The present study identified a complex network of oxylipins, bile acids, lysophospholipids and endocannabinoids deregulated in plasma upon lipopolysaccharide challenge, introduces platelets as powerful inflammatory modulators and suggests that dietary antioxidant supplementation hardly interferes with the induction of inflammatory processes, but may rather support the resolution of inflammation.
Institute
University of Vienna
DepartmentDepartment of Analytical Chemistry
LaboratoryGerner lab
Last NameHagn
First NameGerhard
AddressWähringerstraße 38, 1090 Vienna, Austria
Emailgerhard.hagn@univie.ac.at
Phone+43 1 4277 52375
Submit Date2024-03-18
Raw Data AvailableYes
Raw Data File Type(s)mzML, raw(Thermo)
Analysis Type DetailLC-MS
Release Date2025-06-02
Release Version1
Gerhard Hagn Gerhard Hagn
https://dx.doi.org/10.21228/M8NX50
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN005150
Chromatography ID CH003898
MS ID MS004886
Analysis type MS
Chromatography type Reversed phase
Chromatography system Thermo Vanquish
Column Phenomenex Kinetex XB-C18 (150 x 2.1mm, 2.6um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive HF hybrid Orbitrap
Ion Mode NEGATIVE
Units normalized AUC

Chromatography:

Chromatography ID:CH003898
Chromatography Summary:For LC-MS analyses, analytes were separated using a Thermo Scientific Vanquish (UHPLC) system equipped with a Kinetex C18-column (2.6 µm, XB-C18, 100 A° , LC Column 150 * 2.1 mm; Phenomenex) applying a gradient flow profile (mobile phase A: H2O + 0.2% FA, mobile phase B: ACN:MeOH (vol% 90:10) + 0.2% FA) starting at 35% B and increasing to 90% B (1–10 min), further increasing to 99% B within 0.5 min and held for 5 min. Solvent B was then decreased to the initial level of 35% within 0.5 min and the column was equilibrated for 4 min, resulting in a total run time of 20 min. The flow rate was kept at 200 µL min-1 and the column oven temperature at 40°C. The injection volume was 20 µL and all samples were analysed in technical duplicates.
Instrument Name:Thermo Vanquish
Column Name:Phenomenex Kinetex XB-C18 (150 x 2.1mm, 2.6um)
Column Temperature:40
Flow Gradient:0min with 35% B to 90% B (1–10 min), further increasing to 99% B within 0.5 min and held for 5 min. Solvent B was then decreased to the initial level of 35% within 0.5 min and the column was equilibrated for 4 min, resulting in a total run time of 20 min.
Flow Rate:200 µL/min
Solvent A:100% water; 0.2% formic acid
Solvent B:90% acetonitrile/10% methanol; 0.2% formic acid
Chromatography Type:Reversed phase
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