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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.accessioned2020-03-17T07:09:50Z
dc.date.available2020-03-17T07:09:50Z
dc.date.issued2020-03-03
dc.date.submitted2019-10-25
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/303540
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.languageen
dc.publisherFrontiers Media S.A.
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectPhysiology
dc.subject2-hydroxyglutarate
dc.subjectendotoxemia
dc.subjectsepsis
dc.subjecthypothermia
dc.subject2-hydroxygluterate dehydrogenase
dc.subjectiNOS
dc.title2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia
dc.typeArticle
dc.date.updated2020-03-17T07:09:49Z
prism.publicationNameFrontiers in Physiology
prism.volume11
dc.identifier.doi10.17863/CAM.50617
dcterms.dateAccepted2020-02-11
rioxxterms.versionofrecord10.3389/fphys.2020.00147
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn1664-042X


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