期刊
CRITICAL CARE
卷 26, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13054-022-04174-y
关键词
Metabolomics; N-formylmethionine; Critical illness; Acylcarnitine; Metabolic shift; Pentose phosphate pathway; Branched chain amino acids
资金
- Foundation for the National Institutes of Health (NIH)/National Center for Advancing Translational Sciences [KL2-TR-002385, R01 HL123915]
- NIH [R01 GM115774, R01 HL152083, R01 HL114839, R01 HL142093, R01 GM115605.]
- European Society for Clinical Nutrition and Metabolism (ESPEN)
- Fresenius Kabi (Germany)
- Austrian National Bank (Jubilaumsfonds) [14143]
- Landspitali University Hospital Science Fund [A2021-03]
This study found that in critically ill patients, the level of N-formylmethionine in the blood is associated with changes in metabolites and an increase in 28-day mortality. Increased levels of N-formylmethionine lead to incomplete mitochondrial fatty acid oxidation, increased branched chain amino acid metabolism, and activation of the pentose phosphate pathway.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据