Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Sigurdsson, MI; Kobayashi, H; Amrein, K; Nakahira, K; Rogers, AJ; Pinilla-Vera, M; Baron, RM; Fredenburgh, LE; Lasky-Su, JA; Christopher, KB.
Circulating N-formylmethionine and metabolic shift in critical illness: a multicohort metabolomics study.
CRIT CARE. 2022; 26(1): 321
Doi: 10.1186/s13054-022-04174-y
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- Co-Autor*innen der Med Uni Graz
- Amrein Karin
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult - administration & dosage
- Female - administration & dosage
- Humans - administration & dosage
- Amino Acids, Branched-Chain - administration & dosage
- Critical Illness - administration & dosage
- Fatty Acids - administration & dosage
- Hospital Mortality - administration & dosage
- Intensive Care Units - administration & dosage
- Kynurenine - administration & dosage
- Metabolomics - methods
- N-Formylmethionine - administration & dosage
- Clinical Trials as Topic - administration & dosage
- Find related publications in this database (Keywords)
- Metabolomics
- N-formylmethionine
- Critical illness
- Acylcarnitine
- Metabolic shift
- Pentose phosphate pathway
- Branched chain amino acids