Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction
Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction
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DOI：
10.1152/ajpendo.00117.2011
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发表时间：
2012-05-01
影响因子：
5.1
通讯作者：
Arnould, Thierry
中科院分区：
文献类型：
--
作者：
De Pauw, Aurelia;Demine, Stephane;Arnould, Thierry
De Pauw A、Demine S、Tejerina S、Dieu M、Delaive E、Kel A、Renard P、Raes M、Arnould T。轻度线粒体解偶联不影响线粒体生物发生，但下调脂肪细胞中的丙酮酸羧化酶：甘油三酯含量降低的作用。 Am J Physiol Endocrinol Metab 302：E1123-E1141，2012。首次发表于 2012 年 2 月 21 日； doi:10.1152/ajpendo.00117.2011.-在脂肪细胞中，已知线粒体解偶联会引发甘油三酯损失，与 TNF α（一种促炎细胞因子）诱导的甘油三酯损失相当。然而，线粒体解偶联对线粒体丰度/组成的影响及其与脂肪细胞中甘油三酯含量的关系在很大程度上尚不清楚。在这项工作中，通过定量和定性方法研究了 FCCP 触发的轻度线粒体解偶联对 3T3-L1 脂肪细胞线粒体群的影响。我们发现，轻度线粒体解偶联不会刺激脂肪细胞中的线粒体生物合成，但会诱导以线粒体蛋白含量定量改变为特征的适应性细胞反应。 TNF α 和 FCCP 处理的脂肪细胞的线粒体中超氧阴离子自由基水平均增加，而线粒体 DNA 拷贝数仅在 TNF α 处理的细胞中显着更高。亚蛋白质组分析表明，TNF α 和 FCCP 处理的脂肪细胞线粒体中丙酮酸羧化酶的丰度显着降低。功能研究表明，这种脂质代谢主要酶的过度表达能够防止暴露于线粒体解偶联或 TNF α 的脂肪细胞中甘油三酯含量的降低。这些结果表明线粒体解偶联的作用可能限制脂肪细胞中甘油三酯的积累的新机制。
De Pauw A, Demine S, Tejerina S, Dieu M, Delaive E, Kel A, Renard P, Raes M, Arnould T. Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction. Am J Physiol Endocrinol Metab 302: E1123-E1141, 2012. First published February 21, 2012; doi:10.1152/ajpendo.00117.2011.-In adipocytes, mitochondrial uncoupling is known to trigger a triglyceride loss comparable with the one induced by TNF alpha, a proinflammatory cytokine. However, the impact of a mitochondrial uncoupling on the abundance/composition of mitochondria and its connection with triglyceride content in adipocytes is largely unknown. In this work, the effects of a mild mitochondrial uncoupling triggered by FCCP were investigated on the mitochondrial population of 3T3-L1 adipocytes by both quantitative and qualitative approaches. We found that mild mitochondrial uncoupling does not stimulate mitochondrial biogenesis in adipocytes but induces an adaptive cell response characterized by quantitative modifications of mitochondrial protein content. Superoxide anion radical level was increased in mitochondria of both TNF alpha- and FCCP-treated adipocytes, whereas mitochondrial DNA copy number was significantly higher only in TNF alpha-treated cells. Subproteomic analysis revealed that the abundance of pyruvate carboxylase was reduced significantly in mitochondria of TNF alpha- and FCCP-treated adipocytes. Functional study showed that overexpression of this major enzyme of lipid metabolism is able to prevent the triglyceride content reduction in adipocytes exposed to mitochondrial uncoupling or TNF alpha. These results suggest a new mechanism by which the effects of mitochondrial uncoupling might limit triglyceride accumulation in adipocytes.