Khaliq, W;
Grossmann, P;
Neugebauer, S;
Kleyman, A;
Domizi, R;
Calcinaro, S;
Brealey, D;
... Bauer, M; + view all
(2020)
Lipid metabolic signatures deviate in sepsis survivors compared to non-survivors.
Computational and Structural Biotechnology Journal
, 18
pp. 3678-3691.
10.1016/j.csbj.2020.11.009.
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Abstract
Sepsis remains a major cause of death despite advances in medical care. Metabolic deregulation is an important component of the survival process. Metabolomic analysis allows profiling of critical metabolic functions with the potential to classify patient outcome. Our prospective longitudinal characterization of 33 septic and non-septic critically ill patients showed that deviations, independent of direction, in plasma levels of lipid metabolites were associated with sepsis mortality. We identified a coupling of metabolic signatures between liver and plasma of a rat sepsis model that allowed us to apply a human kinetic model of mitochondrial beta-oxidation to reveal differing enzyme concentrations for medium/short-chain hydroxyacyl-CoA dehydrogenase (elevated in survivors) and crotonase (elevated in non-survivors). These data suggest a need to monitor cellular energy metabolism beyond the available biomarkers. A loss of metabolic adaptation appears to be reflected by an inability to maintain cellular (fatty acid) metabolism within a “corridor of safety”.
| Type: | Article |
|---|---|
| Title: | Lipid metabolic signatures deviate in sepsis survivors compared to non-survivors |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.csbj.2020.11.009 |
| Publisher version: | http://dx.doi.org/10.1016/j.csbj.2020.11.009 |
| Language: | English |
| Additional information: | © 2020 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Sepsis, Metabolomics, Safety corridor, Beta-oxidation, Fatty acid metabolism, Energy metabolism, FATTY-ACID OXIDATION, PNEUMONIA, PATHWAYS, MODEL |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10124240 |
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