Circulating N-formylmethionine and metabolic shift in critical illness: a multicohort metabolomics study

Background Cell stress promotes degradation of mitochondria which release danger-associated molecular patterns that are catabolized to N -formylmethionine. We hypothesized that in critically ill adults, the response to N -formylmethionine is associated with increases in metabolomic shift-related met...

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Vydáno v:Critical Care Ročník 26; číslo 1; s. 321 - 13
Hlavní autoři: Sigurdsson, Martin Ingi, Kobayashi, Hirotada, Amrein, Karin, Nakahira, Kiichi, Rogers, Angela J., Pinilla-Vera, Mayra, Baron, Rebecca M., Fredenburgh, Laura E., Lasky-Su, Jessica A., Christopher, Kenneth B.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Springer Science and Business Media LLC 19.10.2022
BioMed Central
BioMed Central Ltd
BMC
Témata:
Acylcarnitine
Adult
Amino Acids, Branched-Chain
Care and treatment
Clinical Trials as Topic
Critical Care Medicine
Critical Illness
Critically ill
Emergency Medicine
Fatty Acids
Female
Health aspects
Hospital Mortality
Humans
Intensive
Intensive Care Units
Kynurenine
Medical emergencies. Critical care. Intensive care. First aid
Medicine
Medicine & Public Health
Metabolic shift
Metabolomics
Metabolomics - methods
Methionine
N-Formylmethionine
Pentose phosphate pathway
Prognosis
RC86-88.9
Metabolic shift
Metabolomics
Critical illness
Branched chain amino acids
formylmethionine
Acylcarnitine
Pentose phosphate pathway
N-formylmethionine
ISSN:1364-8535, 1466-609X, 1364-8535, 1466-609X
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Shrnutí:Background Cell stress promotes degradation of mitochondria which release danger-associated molecular patterns that are catabolized to N -formylmethionine. We hypothesized that in critically ill adults, the response to N -formylmethionine is associated with increases in metabolomic shift-related metabolites and increases in 28-day mortality. Methods We performed metabolomics analyses on plasma from the 428-subject Correction of Vitamin D Deficiency in Critically Ill Patients trial (VITdAL-ICU) cohort and the 90-subject Brigham and Women’s Hospital Registry of Critical Illness (RoCI) cohort. In the VITdAL-ICU cohort, we analyzed 983 metabolites at Intensive Care Unit (ICU) admission, day 3, and 7. In the RoCI cohort, we analyzed 411 metabolites at ICU admission. The association between N -formylmethionine and mortality was determined by adjusted logistic regression. The relationship between individual metabolites and N -formylmethionine abundance was assessed with false discovery rate correction via linear regression, linear mixed-effects, and Gaussian graphical models. Results Patients with the top quartile of N -formylmethionine abundance at ICU admission had a significantly higher adjusted odds of 28-day mortality in the VITdAL-ICU (OR, 2.4; 95%CI 1.5–4.0; P  = 0.001) and RoCI cohorts (OR, 5.1; 95%CI 1.4–18.7; P  = 0.015). Adjusted linear regression shows that with increases in N -formylmethionine abundance at ICU admission, 55 metabolites have significant differences common to both the VITdAL-ICU and RoCI cohorts. With increased N -formylmethionine abundance, both cohorts had elevations in individual short-chain acylcarnitine, branched chain amino acid, kynurenine pathway, and pentose phosphate pathway metabolites. Conclusions The results indicate that circulating N -formylmethionine promotes a metabolic shift with heightened mortality that involves incomplete mitochondrial fatty acid oxidation, increased branched chain amino acid metabolism, and activation of the pentose phosphate pathway. Graphic Abstract
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1364-8535
1466-609X
1364-8535
1466-609X
DOI:10.1186/s13054-022-04174-y