期刊
FRONTIERS IN PHYSIOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2020.00147
关键词
2-hydroxyglutarate; endotoxemia; sepsis; hypothermia; 2-hydroxygluterate dehydrogenase; iNOS
类别
资金
- Wellcome Trust [WT092738MA]
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.
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