Article
2-hydroxyglutarate metabolism is altered in an in vivo model of LPS induced endotoxemia
Author/s | Fitzpatrick, S. F.
Lambden, S. Macías, David ![]() ![]() ![]() ![]() ![]() ![]() ![]() Puthucheary, Z. Pietsch, S. Mendil, L. |
Department | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Publication Date | 2020 |
Deposit Date | 2023-07-20 |
Published in |
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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) ... 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. © Copyright © 2020 Fitzpatrick, Lambden, Macias, Puthucheary, Pietsch, Mendil, McPhail and Johnson. |
Funding agencies | Wellcome Trust |
Project ID. | WT092738MA
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Citation | Fitzpatrick, S.F., Lambden, S., Macías, D., Puthucheary, Z., Pietsch, S. y Mendil, L. (2020). 2-hydroxyglutarate metabolism is altered in an in vivo model of LPS induced endotoxemia. Frontiers in Physiology, 11. https://doi.org/10.3389/fphys.2020.00147. |
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