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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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.
| Study ID | ST003137 |
| Study Title | Lipid 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 Summary | While 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 |
| Department | Department of Analytical Chemistry |
| Laboratory | Gerner lab |
| Last Name | Hagn |
| First Name | Gerhard |
| Address | Währingerstraße 38, 1090 Vienna, Austria |
| gerhard.hagn@univie.ac.at | |
| Phone | +43 1 4277 52375 |
| Submit Date | 2024-03-18 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML, raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-06-02 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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 |
MS:
| MS ID: | MS004886 |
| Analysis ID: | AN005150 |
| Instrument Name: | Thermo Q Exactive HF hybrid Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | The Vanquish UHPLC system was coupled to a Q ExactiveTM HF Quadrupole-OrbitrapTM high-resolution mass spectrometer (Thermo Fisher Scientific, Austria), equipped with a HESI source for negative ionization to perform the mass spectrometric analysis. The MS scan range was 250-700 m/z with a resolution of 60,000 (at m/z 200) on the MS1 level. A Top 2 method was applied for fragmentation (HCD 24 normalized collision energy), preferable 33 m/z values specific for well-known eicosanoids and precursor molecules from an inclusion list. The resulting fragments were analysed on the MS2 level at a resolution of 15,000 (at m/z 200). Operating in negative ionization mode, a spray voltage of 3.5 kV and a capillary temperature of 253°C were applied. Sheath gas was set to 46 and the auxiliary gas to 10 (arbitrary units). |
| Ion Mode: | NEGATIVE |