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

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dc.contributor Landspitali - The National University Hospital of Iceland
dc.contributor.author Sigurðsson, Martin Ingi
dc.contributor.author Kobayashi, Hirotada
dc.contributor.author Amrein, Karin
dc.contributor.author Nakahira, Kiichi
dc.contributor.author Rogers, Angela J.
dc.contributor.author Pinilla-Vera, Mayra
dc.contributor.author Baron, Rebecca M.
dc.contributor.author Fredenburgh, Laura E.
dc.contributor.author Lasky-Su, Jessica A.
dc.contributor.author Christopher, Kenneth B.
dc.date.accessioned 2022-11-04T01:04:00Z
dc.date.available 2022-11-04T01:04:00Z
dc.date.issued 2022-10-19
dc.identifier.citation Sigurðsson , M I , Kobayashi , H , Amrein , K , Nakahira , K , Rogers , A J , Pinilla-Vera , M , Baron , R M , Fredenburgh , L E , Lasky-Su , J A & Christopher , K B 2022 , ' Circulating N-formylmethionine and metabolic shift in critical illness : a multicohort metabolomics study ' , Critical Care , vol. 26 , no. 1 , 321 , pp. 321 . https://doi.org/10.1186/s13054-022-04174-y
dc.identifier.issn 1364-8535
dc.identifier.other 63667088
dc.identifier.other 6558090c-b9ee-4b63-baf4-46671c1c6eb6
dc.identifier.other 85140223642
dc.identifier.other 36261854
dc.identifier.other unpaywall: 10.1186/s13054-022-04174-y
dc.identifier.uri https://hdl.handle.net/20.500.11815/3580
dc.description Funding Information: KN is supported by Foundation for the National Institutes of Health (NIH)/National Center for Advancing Translational Sciences grant KL2-TR-002385, R01 HL123915. AJR is supported by NIH grant R01 HL152083. LEF is supported by NIH grant R01 HL114839. RMB is supported by NIH grants R01 HL142093 and R01 GM115605. KBC is supported by NIH grant R01 GM115774. The VITdAL-ICU trial was supported by the European Society for Clinical Nutrition and Metabolism (ESPEN), a research grant including provision of study medication from Fresenius Kabi (Germany), and the Austrian National Bank (Jubiläumsfonds, Project Nr. 14143). Landspitali University Hospital Science Fund: A2021-03 Publisher Copyright: © 2022, The Author(s). © 2022. The Author(s).
dc.description.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.
dc.format.extent 1632266
dc.format.extent 321
dc.language.iso en
dc.relation.ispartofseries Critical Care; 26(1)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Svæfinga- og gjörgæslulæknisfræði
dc.subject Acylcarnitine
dc.subject Branched chain amino acids
dc.subject Critical illness
dc.subject Metabolic shift
dc.subject Metabolomics
dc.subject N-formylmethionine
dc.subject Pentose phosphate pathway
dc.subject Intensive Care Units
dc.subject Fatty Acids
dc.subject Hospital Mortality
dc.subject Humans
dc.subject Critical Illness
dc.subject Clinical Trials as Topic
dc.subject Amino Acids, Branched-Chain
dc.subject Kynurenine
dc.subject Adult
dc.subject Female
dc.subject N-Formylmethionine
dc.subject Metabolomics/methods
dc.subject Critical Care and Intensive Care Medicine
dc.title Circulating N-formylmethionine and metabolic shift in critical illness : a multicohort metabolomics study
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.doi 10.1186/s13054-022-04174-y
dc.relation.url http://www.scopus.com/inward/record.url?scp=85140223642&partnerID=8YFLogxK
dc.contributor.department Perioperative Services
dc.contributor.department Faculty of Medicine

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