Summary of Study ST003982

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 IDST003982
Study TitleMitochondrial pyruvate metabolism is disturbed and contributes to hyperlactatemia and lethality in sepsis - Liver, Plasma, Skeletal muscle
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

Select appropriate tab below to view additional metadata details:

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:SU004119
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
SA454355MCF001167_LN05Liver CLP 13C pyruvate
SA454356MCF001167_LN29Liver CLP 13C pyruvate
SA454357MCF001167_LN26Liver CLP 13C pyruvate
SA454358MCF001167_LN11Liver CLP 13C pyruvate
SA454359MCF001167_LN20Liver CLP 13C pyruvate
SA454360MCF001167_LN32Liver CLP PBS
SA454361MCF001167_LN17Liver Sham 13C pyruvate
SA454362MCF001167_LN08Liver Sham 13C pyruvate
SA454363MCF001167_LN23Liver Sham 13C pyruvate
SA454364MCF001167_LN14Liver Sham 13C pyruvate
SA454365MCF001167_LN02Liver Sham 13C pyruvate
SA454366MCF001167_LN35Liver Sham PBS
SA454367MCF001167_LN28Plasma CLP 13C pyruvate
SA454368MCF001167_LN25Plasma CLP 13C pyruvate
SA454369MCF001167_LN19Plasma CLP 13C pyruvate
SA454370MCF001167_LN04Plasma CLP 13C pyruvate
SA454371MCF001167_LN10Plasma CLP 13C pyruvate
SA454372MCF001167_LN31Plasma CLP PBS
SA454373MCF001167_LN16Plasma Sham 13C pyruvate
SA454374MCF001167_LN07Plasma Sham 13C pyruvate
SA454375MCF001167_LN01Plasma Sham 13C pyruvate
SA454376MCF001167_LN13Plasma Sham 13C pyruvate
SA454377MCF001167_LN22Plasma Sham 13C pyruvate
SA454378MCF001167_LN34Plasma Sham PBS
SA454379MCF001167_LN12Skeletal muscle CLP 13C pyruvate
SA454380MCF001167_LN21Skeletal muscle CLP 13C pyruvate
SA454381MCF001167_LN06Skeletal muscle CLP 13C pyruvate
SA454382MCF001167_LN30Skeletal muscle CLP 13C pyruvate
SA454383MCF001167_LN27Skeletal muscle CLP 13C pyruvate
SA454384MCF001167_LN33Skeletal muscle CLP PBS
SA454385MCF001167_LN24Skeletal muscle Sham 13C pyruvate
SA454386MCF001167_LN09Skeletal muscle Sham 13C pyruvate
SA454387MCF001167_LN18Skeletal muscle Sham 13C pyruvate
SA454388MCF001167_LN15Skeletal muscle Sham 13C pyruvate
SA454389MCF001167_LN03Skeletal muscle Sham 13C pyruvate
SA454390MCF001167_LN36Skeletal muscle Sham PBS
Showing results 1 to 36 of 36

Collection:

Collection ID:CO004112
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 (liver, skeletal muscle and plasma) were isolated and snapfrozen in liquid nitrogen and stored at -80°C for further analysis.
Sample Type:Liver, Plasma, Skeletal muscle
Additives:Additional sample source/type: muscle and plasma

Treatment:

Treatment ID:TR004128
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 (liver, skeletal muscle and plasma) were isolated and snapfrozen in liquid nitrogen and stored at -80°C for further analysis.

Sample Preparation:

Sampleprep ID:SP004125
Sampleprep Summary:Liver, skeletal muscle and plasma 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).
Processing Storage Conditions:-80℃

Chromatography:

Chromatography ID:CH004977
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:Start: 90% A / 10% B; 2–12 min: linear increase to 60% B; 12–15 min: held at 60% B; 15–25 min: decreased back to 10% B
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:AN006558
Analysis Type:MS
Chromatography ID:CH004977
Num Factors:12
Num Metabolites:67
Units:peak intensity
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