Summary of project PR002492
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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| 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 |
Summary of all studies in project PR002492
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003980 | Glutamate-mediated TCA anaplerosis is increased in septic mitochondria | Mus musculus | Ghent University | MS | 2025-08-14 | 1 | 11 | Uploaded data (2.7G)* |
| ST003981 | Mitochondrial pyruvate metabolism is disturbed in sepsis | Mus musculus | Ghent University | MS | 2025-08-14 | 1 | 22 | Uploaded data (6.4G)* |
| ST003982 | Mitochondrial pyruvate metabolism is disturbed and contributes to hyperlactatemia and lethality in sepsis - Liver, Plasma, Skeletal muscle | Mus musculus | Ghent University | MS | 2025-08-14 | 1 | 36 | Uploaded data (5.4G)* |
| ST003983 | Mitochondrial pyruvate metabolism is disturbed and contributes to hyperlactatemia and lethality in sepsis - Lung, Heart, Spleen, Kidney, RBC | Mus musculus | Ghent University | MS | 2025-08-14 | 1 | 60 | Uploaded data (10.1G)* |
