Circulating N-formylmethionine and metabolic shift in critical illness: a multicohort metabolomics study.
Circulating N-formylmethionine and metabolic shift in critical illness: a multicohort metabolomics study.
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疾病中循环的N-甲米汀和代谢转移：多hort代谢组学研究。
DOI：
10.1186/s13054-022-04174-y
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发表时间：
2022-10-19
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影响因子：
--
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中科院分区：
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--
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细胞应激促进线粒体的降解，释放危险相关的分子模式，分解代谢为n -甲酰基蛋氨酸。我们假设在危重成人中，对n -甲酰基蛋氨酸的反应与代谢组学转移相关代谢物的增加和28天死亡率的增加有关。我们对428名危重患者维生素D缺乏症纠正试验（VITdAL-ICU）队列和90名布莱根妇女医院危重疾病登记处（RoCI）队列的血浆进行了代谢组学分析。在VITdAL-ICU队列中，我们分析了重症监护病房（ICU）入院第3天和第7天的983例代谢物。在RoCI队列中，我们分析了ICU入院时的411种代谢物。n -甲酰蛋氨酸与死亡率之间的关系通过调整后的逻辑回归确定。个体代谢物与n -甲酰蛋氨酸丰度之间的关系通过线性回归、线性混合效应和高斯图形模型进行错误发现率校正来评估。在ICU入院时n -甲酰蛋氨酸丰度最高的患者，在vitda -ICU组（OR, 2.4; 95%CI 1.5-4.0; P = 0.001）和RoCI组（OR, 5.1; 95%CI 1.4-18.7; P = 0.015）中28天死亡率的调整几率显著高于其他组（OR, 2.4; 95%CI 1.5-4.0; P = 0.001）。调整后的线性回归显示，随着ICU入院时n -甲酰基蛋氨酸丰度的增加，55种代谢物在VITdAL-ICU和RoCI队列中都有显著差异。随着n -甲酰蛋氨酸丰度的增加，两个队列中单个短链酰基肉碱、支链氨基酸、犬尿氨酸途径和戊糖磷酸途径代谢物的含量都有所升高。结果表明，循环n -甲酰蛋氨酸促进代谢转变，导致死亡率升高，包括线粒体脂肪酸氧化不完全、支链氨基酸代谢增加和戊糖磷酸途径的激活。在线版本包含补充材料，可在10.1186/s13054-022-04174-y获得。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s13054-022-04174-y.
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影响因子：
11.1
作者：
Scicluna BP
通讯作者：
Scicluna BP
影响因子：
--
作者：
Krumsiek J;Suhre K;Illig T;Adamski J;Theis FJ
通讯作者：
Theis FJ
影响因子：
4
作者：
Do KT;Pietzner M;Rasp DJ;Friedrich N;Nauck M;Kocher T;Suhre K;Mook-Kanamori DO;Kastenmüller G;Krumsiek J
通讯作者：
Krumsiek J
影响因子：
4.6
作者：
Chary S;Amrein K;Lasky-Su JA;Dobnig H;Christopher KB
通讯作者：
Christopher KB
影响因子：
2.4
作者：
Barker, M;Rayens, W
通讯作者：
Rayens, W