Summary of Study ST003983

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 PR002492. The data can be accessed directly via it's Project DOI: 10.21228/M8HV6F 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 IDST003983
Study TitleMitochondrial pyruvate metabolism is disturbed and contributes to hyperlactatemia and lethality in sepsis - Lung, Heart, Spleen, Kidney, RBC
Study SummaryTo determine the source of lactate production in sepsis, lactate dehydrogenase A (LDHA) activity was examined in several organs of sham and cecal ligation and puncture (CLP) mice using 13C3 pyruvate tracer metabolomics assay. Septic heart and skeletal muscle did not show an enhanced 13C labeling of lactate, indicating that LDHA activity is not increased in these tissues and that they are unlikely to be major sources of elevated lactate production in sepsis. Conversely, septic liver, kidney, spleen and lung were characterized by a notably higher 13C-labeling for lactate, indicating elevated local lactate production that may contribute to systemic hyperlactatemia.
Institute
Ghent University
Last NameLibert
First NameClaude
AddressTechnologiepark-Zwijnaarde 71, 9052 Ghent, Belgium
Emailclaude.libert@irc.vib-ugent.be
Phone09/331.37.00
Submit Date2025-06-06
Raw Data AvailableYes
Raw Data File Type(s)mzML, raw(Thermo)
Analysis Type DetailLC-MS
Release Date2025-08-14
Release Version1
Claude Libert Claude Libert
https://dx.doi.org/10.21228/M8HV6F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002492
Project DOI:doi: 10.21228/M8HV6F
Project Title:Unraveling mitochondrial pyruvate dysfunction to mitigate hyperlactatemia and lethality in sepsis
Project Summary:Sepsis, killing 11 million people yearly, is associated with increased lactate production - a metabolite mechanistically linked to mortality - complicating glucose administration in sepsis. To understand the mechanism behind hyperlactatemia, we applied the cecal ligation and puncture (CLP) model and studied all pyruvate processing routes in liver mitochondria during acute sepsis. Our data suggest that mitochondrial pyruvate-driven respiration is nearly nonexistent in sepsis, not due to insufficient pyruvate uptake or carboxylation but due to a dysfunctional pyruvate dehydrogenase complex (PDC). Septic mitochondria compensate by glutamate-mediated TCA anaplerosis, simultaneously converting some pyruvate into alanine via enhanced mitochondrial glutamic pyruvate transaminase (GPT2) activity. Notably, PDC dysfunction is not caused by PDC inactivation per se but by a shortage of its cofactor, thiamine pyrophosphate (TPP). TPP supplementation restores pyruvate oxidation both ex vivo and in vivo and protects mice from sepsis. TPP also allows safe glucose administration in mice, leading to a novel, robust TPP-plus-glucose therapy.
Institute:Ghent University
Department:Inflammation research center - VIB
Laboratory:Mouse Genetics in Inflammation
Last Name:Libert
First Name:Claude
Address:Technologiepark-Zwijnaarde 71, 9052 Ghent, Belgium
Email:claude.libert@irc.vib-ugent.be
Phone:09/331.37.00

Subject:

Subject ID:SU004120
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Treatment condition Tracer condition
SA454391MCF001221_LN47Heart CLP 13C pyruvate
SA454392MCF001221_LN32Heart CLP 13C pyruvate
SA454393MCF001221_LN07Heart CLP 13C pyruvate
SA454394MCF001221_LN17Heart CLP 13C pyruvate
SA454395MCF001221_LN42Heart CLP 13C pyruvate
SA454396MCF001221_LN52Heart CLP PBS
SA454397MCF001221_LN02Heart Sham 13C pyruvate
SA454398MCF001221_LN22Heart Sham 13C pyruvate
SA454399MCF001221_LN37Heart Sham 13C pyruvate
SA454400MCF001221_LN27Heart Sham 13C pyruvate
SA454401MCF001221_LN12Heart Sham 13C pyruvate
SA454402MCF001221_LN57Heart Sham PBS
SA454403MCF001221_LN44Kidney CLP 13C pyruvate
SA454404MCF001221_LN49Kidney CLP 13C pyruvate
SA454405MCF001221_LN09Kidney CLP 13C pyruvate
SA454406MCF001221_LN19Kidney CLP 13C pyruvate
SA454407MCF001221_LN34Kidney CLP 13C pyruvate
SA454408MCF001221_LN54Kidney CLP PBS
SA454409MCF001221_LN29Kidney Sham 13C pyruvate
SA454410MCF001221_LN39Kidney Sham 13C pyruvate
SA454411MCF001221_LN24Kidney Sham 13C pyruvate
SA454412MCF001221_LN04Kidney Sham 13C pyruvate
SA454413MCF001221_LN14Kidney Sham 13C pyruvate
SA454414MCF001221_LN59Kidney Sham PBS
SA454415MCF001221_LN46Lung CLP 13C pyruvate
SA454416MCF001221_LN41Lung CLP 13C pyruvate
SA454417MCF001221_LN31Lung CLP 13C pyruvate
SA454418MCF001221_LN16Lung CLP 13C pyruvate
SA454419MCF001221_LN06Lung CLP 13C pyruvate
SA454420MCF001221_LN51Lung CLP PBS
SA454421MCF001221_LN01Lung Sham 13C pyruvate
SA454422MCF001221_LN26Lung Sham 13C pyruvate
SA454423MCF001221_LN36Lung Sham 13C pyruvate
SA454424MCF001221_LN21Lung Sham 13C pyruvate
SA454425MCF001221_LN11Lung Sham 13C pyruvate
SA454426MCF001221_LN56Lung Sham PBS
SA454427MCF001221_LN50Red blood cells CLP 13C pyruvate
SA454428MCF001221_LN10Red blood cells CLP 13C pyruvate
SA454429MCF001221_LN45Red blood cells CLP 13C pyruvate
SA454430MCF001221_LN20Red blood cells CLP 13C pyruvate
SA454431MCF001221_LN35Red blood cells CLP 13C pyruvate
SA454432MCF001221_LN55Red blood cells CLP PBS
SA454433MCF001221_LN05Red blood cells Sham 13C pyruvate
SA454434MCF001221_LN15Red blood cells Sham 13C pyruvate
SA454435MCF001221_LN30Red blood cells Sham 13C pyruvate
SA454436MCF001221_LN40Red blood cells Sham 13C pyruvate
SA454437MCF001221_LN25Red blood cells Sham 13C pyruvate
SA454438MCF001221_LN60Red blood cells Sham PBS
SA454439MCF001221_LN18Spleen CLP 13C pyruvate
SA454440MCF001221_LN43Spleen CLP 13C pyruvate
SA454441MCF001221_LN48Spleen CLP 13C pyruvate
SA454442MCF001221_LN08Spleen CLP 13C pyruvate
SA454443MCF001221_LN33Spleen CLP 13C pyruvate
SA454444MCF001221_LN53Spleen CLP PBS
SA454445MCF001221_LN03Spleen Sham 13C pyruvate
SA454446MCF001221_LN23Spleen Sham 13C pyruvate
SA454447MCF001221_LN13Spleen Sham 13C pyruvate
SA454448MCF001221_LN38Spleen Sham 13C pyruvate
SA454449MCF001221_LN28Spleen Sham 13C pyruvate
SA454450MCF001221_LN58Spleen Sham PBS
Showing results 1 to 60 of 60

Collection:

Collection ID:CO004113
Collection Summary:Mice were subjected to the cecal ligation and puncture (CLP) (n=5) to induce polymicrobial sepsis and the sham (control) procedure (n=5). After 24h, mice were injected with 13C3, 99% sodium pyruvate (2 g/kg; Buchem B.V. CLM-2440-0.5) or PBS and 90 minutes after injection organs of interest (lungs, kidney, spleen, heart and red blood cells) were isolated and snapfrozen in liquid nitrogen and stored at -80°C for further analysis.
Sample Type:Lung, Heart, Spleen, Kidney, RBC
Additives:Additional sample source/type: spleen, kidney, heart and red blood cells

Treatment:

Treatment ID:TR004129
Treatment Summary:Mice were subjected to the cecal ligation and puncture (CLP) (n=5), as described by Rittirsch et al. (Nature Protocols: 2009;4(1):31-6. doi: 10.1038/nprot.2008.214), to induce polymicrobial sepsis and the sham (control, n=5) procedure. After 24h, mice were injected with 13C3, 99% sodium pyruvate (2 g/kg; Buchem B.V. CLM-2440-0.5) or PBS and 90 minutes after injection organs of interest (lungs, kidney, spleen, heart and red blood cells) were isolated and snapfrozen in liquid nitrogen and stored at -80°C for further analysis.

Sample Preparation:

Sampleprep ID:SP004126
Sampleprep Summary:Lungs, spleen, kidney, heart and red blood cells were isolated 90 minutes after 13C pyruvate or PBS injection, snapfrozen in liquid nitrogen and stored at -80°C until further analysis by the VIB metabolomics core (KU Leuven, Belgium).
Sampleprep Protocol Filename:Protocol_methods_invivo_13Cpyruvate.pdf

Chromatography:

Chromatography ID:CH004978
Methods Filename:Protocol_methods_invivo_13Cpyruvate.pdf
Instrument Name:Thermo Dionex Ultimate 3000
Column Name:Agilent InfinityLab Poroshell 120 HILIC-Z (150 x 2.1mm, 2.7um)
Column Temperature:25°C
Flow Gradient:A linear gradient was carried out starting with 90% solvent A and 10% solvent B. From 2 to 12 min the gradient changed to 60% B. The gradient was kept on 60% B for 3 min and followed by a decrease to 10% B. The chromatography was stopped at 25 min
Flow Rate:0.25 mL/min
Solvent A:100% acetonitrile
Solvent B:100% water; 10 mM sodium acetate (pH 9.3)
Chromatography Type:HILIC

Analysis:

Analysis ID:AN006559
Analysis Type:MS
Analysis Protocol File:Protocol_methods_invivo_13Cpyruvate.pdf
Chromatography ID:CH004978
Num Factors:20
Num Metabolites:71
Units:peak intensity
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