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
Email	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

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Treatment:

Treatment ID:	TR003263
Treatment Summary:	Subjects were recruited by the Department of Clinical Pharmacology at the Medical University of Vienna. The study protocol was approved by the Ethics Committee of the Medical University of Vienna (EC No.: 64/2009) and was conducted in accordance with the guidelines of the Helsinki Declaration. For this randomized, double-masked, placebo-controlled parallel group study, 30 healthy male human individuals were included upon passing a screening examination and signed written informed consent prior to study entry. Subjects with any clinically relevant illness, intake of medication, including vitamin or mineral supplements, or blood donation within 3 weeks prior to the study were excluded and subjects who did not complete the study were replaced. In addition, participants had to abstain from alcohol or caffeine containing beverages within 12 hours prior to each study day of the dual stage controlled clinical intervention study. To induce systemic inflammation and oxidative stress, an intravenous infusion of a bolus containing 2 ng/kg bodyweight Escherichia coli endotoxin known as lipopolysaccharide (LPS; NIH-CC, Bethesda, MD, USA) was used. Full blood was collected using EDTA-anticoagulated collection tubes at baseline (BL), 60 min, 120 min, 240 min and 480 min after LPS infusion and plasma was obtained immediately by centrifugation at 4 °C at 2000 g for 10 min. After centrifugation, all samples were immediately frozen in pre-labelled Eppendorf safe-lock tubes at -80 °C until analysis. After this first stage, participants were randomly assigned to take either the omega-3 fatty acid containing food supplement Vitamac (n = 17; Croma Pharma GmbH, Korneuburg, Austria) or matching lactose and wheat starch containing placebo capsules (n = 13) for 14 days. After the 14 days intervention, all participants were treated again with LPS in the second stage and plasma was collected at baseline (BL), 60 min, 120 min, 240 min and 480 min after LPS infusion applying the same protocol as described for the first stage.

Treatment ID:

TR003263

Treatment Summary:

Subjects were recruited by the Department of Clinical Pharmacology at the Medical University of Vienna. The study protocol was approved by the Ethics Committee of the Medical University of Vienna (EC No.: 64/2009) and was conducted in accordance with the guidelines of the Helsinki Declaration. For this randomized, double-masked, placebo-controlled parallel group study, 30 healthy male human individuals were included upon passing a screening examination and signed written informed consent prior to study entry. Subjects with any clinically relevant illness, intake of medication, including vitamin or mineral supplements, or blood donation within 3 weeks prior to the study were excluded and subjects who did not complete the study were replaced. In addition, participants had to abstain from alcohol or caffeine containing beverages within 12 hours prior to each study day of the dual stage controlled clinical intervention study. To induce systemic inflammation and oxidative stress, an intravenous infusion of a bolus containing 2 ng/kg bodyweight Escherichia coli endotoxin known as lipopolysaccharide (LPS; NIH-CC, Bethesda, MD, USA) was used. Full blood was collected using EDTA-anticoagulated collection tubes at baseline (BL), 60 min, 120 min, 240 min and 480 min after LPS infusion and plasma was obtained immediately by centrifugation at 4 °C at 2000 g for 10 min. After centrifugation, all samples were immediately frozen in pre-labelled Eppendorf safe-lock tubes at -80 °C until analysis. After this first stage, participants were randomly assigned to take either the omega-3 fatty acid containing food supplement Vitamac (n = 17; Croma Pharma GmbH, Korneuburg, Austria) or matching lactose and wheat starch containing placebo capsules (n = 13) for 14 days. After the 14 days intervention, all participants were treated again with LPS in the second stage and plasma was collected at baseline (BL), 60 min, 120 min, 240 min and 480 min after LPS infusion applying the same protocol as described for the first stage.