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2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia

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2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia. / Fitzpatrick, Susan F.; Lambden, Simon; Macias, David; Puthucheary, Zudin; Pietsch, Sandra; Mendil, Lee; McPhail, Mark J.W.; Johnson, Randall S.

In: Frontiers in Physiology, Vol. 11, 147, 03.03.2020.

Research output: Contribution to journalArticle

Harvard

Fitzpatrick, SF, Lambden, S, Macias, D, Puthucheary, Z, Pietsch, S, Mendil, L, McPhail, MJW & Johnson, RS 2020, '2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia', Frontiers in Physiology, vol. 11, 147. https://doi.org/10.3389/fphys.2020.00147

APA

Fitzpatrick, S. F., Lambden, S., Macias, D., Puthucheary, Z., Pietsch, S., Mendil, L., ... Johnson, R. S. (2020). 2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia. Frontiers in Physiology, 11, [147]. https://doi.org/10.3389/fphys.2020.00147

Vancouver

Fitzpatrick SF, Lambden S, Macias D, Puthucheary Z, Pietsch S, Mendil L et al. 2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia. Frontiers in Physiology. 2020 Mar 3;11. 147. https://doi.org/10.3389/fphys.2020.00147

Author

Fitzpatrick, Susan F. ; Lambden, Simon ; Macias, David ; Puthucheary, Zudin ; Pietsch, Sandra ; Mendil, Lee ; McPhail, Mark J.W. ; Johnson, Randall S. / 2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia. In: Frontiers in Physiology. 2020 ; Vol. 11.

Bibtex Download

@article{ce593b0bd3274e9696f2172c7c734e58,
title = "2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia",
abstract = "The 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.",
keywords = "2-hydroxyglutarate, 2-hydroxygluterate dehydrogenase, endotoxemia, hypothermia, iNOS, sepsis",
author = "Fitzpatrick, {Susan F.} and Simon Lambden and David Macias and Zudin Puthucheary and Sandra Pietsch and Lee Mendil and McPhail, {Mark J.W.} and Johnson, {Randall S.}",
year = "2020",
month = "3",
day = "3",
doi = "10.3389/fphys.2020.00147",
language = "English",
volume = "11",
journal = "Frontiers in Physiology",
issn = "1664-042X",
publisher = "Frontiers",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - 2-Hydroxyglutarate Metabolism Is Altered in an in vivo Model of LPS Induced Endotoxemia

AU - Fitzpatrick, Susan F.

AU - Lambden, Simon

AU - Macias, David

AU - Puthucheary, Zudin

AU - Pietsch, Sandra

AU - Mendil, Lee

AU - McPhail, Mark J.W.

AU - Johnson, Randall S.

PY - 2020/3/3

Y1 - 2020/3/3

N2 - The 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.

AB - The 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.

KW - 2-hydroxyglutarate

KW - 2-hydroxygluterate dehydrogenase

KW - endotoxemia

KW - hypothermia

KW - iNOS

KW - sepsis

UR - http://www.scopus.com/inward/record.url?scp=85082670840&partnerID=8YFLogxK

U2 - 10.3389/fphys.2020.00147

DO - 10.3389/fphys.2020.00147

M3 - Article

AN - SCOPUS:85082670840

VL - 11

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

M1 - 147

ER -

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