Polymicrobial sepsis is associated with decreased hepatic oxidative phosphorylation and an altered metabolic profile.
Polymicrobial sepsis is associated with decreased hepatic oxidative phosphorylation and an altered metabolic profile.
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DOI：
10.1016/j.jss.2013.08.007
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发表时间：
2014-01
影响因子：
2.2
通讯作者：
Zuckerbraun, Brian S.
中科院分区：
文献类型：
--
作者：
Whelan, Sean P.;Carchman, Evie H.;Kautza, Benjamin;Nassour, Ibrahim;Mollen, Kevin;Escobar, Daniel;Gomez, Hernando;Rosengart, Matthew A.;Shiva, Sruti;Zuckerbraun, Brian S.
脓毒症引起的器官衰竭是世界范围内的主要死亡原因。线粒体和代谢反应是细胞整体反应的核心，因此也是器官和生物体的核心。代谢中的适应性反应对细胞水平的恢复至关重要。这些研究的目的是检验脓毒症与有氧呼吸减少和肝脏显著代谢变化相关的假设。C57 BL/6小鼠用21号针进行盲肠结扎和穿刺（CLP）或不进行CLP的手术。在手术后0-24小时对小鼠实施安乐死，并收获肝组织。测定组织耗氧量和线粒体复合体活性。在8 h时间点（n = 8/组）对311种代谢物进行了总体生化特征分析，并由Metabolon（达勒姆，北卡罗来纳州）通过气相色谱-质谱和液相色谱串联质谱平台进行了分析。本文还研究了脂多糖（LPS）对原代小鼠肝细胞有氧和无氧呼吸的影响。CLP在体内或LPS在体外导致肝耗氧量显着下降。在12 h时测得氧化磷酸化显著降低。LPS还导致肝细胞无氧呼吸显著增加。有趣的是，代谢组学分析导致肝脏中的代谢从基于碳水化合物的能量转变为脂肪酸和氨基酸的利用。这包括每个三羧酸循环中间体和衍生物的增加，表明脂肪酸β-氧化和氨基酸回补贡献的循环通量增加。脓毒症导致代谢反应和特征与无氧呼吸增加一致，其发生在血流动力学显著变化之前。细胞和器官的代谢反应可能是防止器官衰竭和死亡的重要适应性反应。
Organ failure in sepsis accounts for significant mortality worldwide. Mitochondrial and metabolic responses are central to the overall response of the cell, and thus of the organ and organism. Adaptive responses in metabolism are critical to the recovery at the cellular level. The purpose of these investigations was to test the hypothesis that sepsis is associated with decreased aerobic respiration and significant metabolic changes in the liver. C57BL/6 mice underwent cecal ligation and puncture (CLP) with a 21 gauge needle or an operation without CLP. Mice were euthanized from 0–24 h after the procedure and liver tissue was harvested. Tissue oxygen consumption and mitochondrial complex activity were measured. Global biochemical profiles of 311 metabolites were performed at the 8-h time point (n = 8/group) and analyzed by gas chromatography–mass spectrometry and liquid chromatography tandem mass spectrometry platforms by Metabolon (Durham, North Carolina). The influence of lipopolysaccharide (LPS) on aerobic and anaerobic respiration in primary mouse hepatocytes was also investigated. CLP in vivo or LPS in vitro resulted in a significant decrease in hepatic oxygen consumption. There was a significant decrease in oxidative phosphorylation measured at 12 h. LPS also resulted in a significant increase in anaerobic respiration in hepatocytes. Interestingly, the metabolomic analysis resulted in a metabolic shift in the liver from carbohydrate-based energy to utilization of fatty acids and amino acids. This included an increase in every tricarboxylic acid cycle intermediate and derivative, suggesting an increased flux into the cycle from fatty acid beta-oxidation and anaplerotic contributions from amino acids. Sepsis results in a metabolic response and profile consistent with increased anaerobic respiration, which occurs prior to significant changes in hemodynamics. The metabolic responses of cells and organs may be important adaptive responses to prevent organ failure and death.
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DOI：
10.1152/ajpregu.00432.2003
发表时间：
2004-03-01
影响因子：
2.8
作者：
Brealey, D;Karyampudi, S;Singer, M
通讯作者：
Singer, M
影响因子：
5.7
作者：
Singer, Mervyn
通讯作者：
Singer, Mervyn
影响因子：
120.7
作者：
HOTCHKISS, RS;KARL, IE
通讯作者：
KARL, IE
影响因子：
9
作者：
ASKANAZI, J;CARPENTIER, YA;KINNEY, JM
通讯作者：
KINNEY, JM
影响因子：
3.4
作者：
GIOVANNINI, I;BOLDRINI, G;CASTIGLIONI, G
通讯作者：
CASTIGLIONI, G