Show simple item record

dc.contributor.authorFitzpatrick, Susan F
dc.contributor.authorLambden, Simon
dc.contributor.authorMacias, David
dc.contributor.authorPuthucheary, Zudin
dc.contributor.authorPietsch, Sandra
dc.contributor.authorMendil, Lee
dc.contributor.authorMcPhail, Mark J W
dc.contributor.authorJohnson, Randall S
dc.date.accessioned2020-04-21T00:24:30Z
dc.date.available2020-04-21T00:24:30Z
dc.date.issued2020-03-03
dc.identifier.issn1664-042X
dc.identifier.otherPMC7063103
dc.identifier.other32194434
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/304567
dc.description.abstractThe metabolic response to endotoxemia closely mimics those seen in sepsis. Here, we show that the urinary excretion of the metabolite 2-hydroxyglutarate (2HG) is dramatically suppressed following lipopolysaccharide (LPS) administration in vivo, and in human septic patients. We further show that enhanced activation of the enzymes responsible for 2-HG degradation, D- and L-2-HGDH, underlie this effect. To determine the role of supplementation with 2HG, we carried out co-administration of LPS and 2HG. This co-administration in mice modulates a number of aspects of physiological responses to LPS, and in particular, protects against LPS-induced hypothermia. Our results identify a novel role for 2HG in endotoxemia pathophysiology, and suggest that this metabolite may be a critical diagnostic and therapeutic target for sepsis.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1664-042X
dc.sourcenlmid: 101549006
dc.subjectSepsis
dc.subjectHypothermia
dc.subjectiNOS
dc.subjectendotoxemia
dc.subject2-Hydroxyglutarate
dc.subject2-Hydroxygluterate Dehydrogenase
dc.title2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia.
dc.typeArticle
dc.date.updated2020-04-21T00:24:29Z
prism.publicationNameFrontiers in Physiology
prism.volume11
dc.identifier.doi10.17863/CAM.51649
rioxxterms.versionofrecord10.3389/fphys.2020.00147
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
pubs.funder-project-idWellcome Trust (WT092738MA)


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International