Flamment Mélissa, Arvier Matthieu, Gallois Yves, Simard Gilles, Malthièry Yves, Ritz Patrick, Ducluzeau Pierre-Henri
INSERM, U694, CHU Angers, 4 rue Larrey, F-49033 Angers, France.
Biochimie. 2008 Sep;90(9):1407-13. doi: 10.1016/j.biochi.2008.05.003. Epub 2008 May 15.
The relationship between insulin resistance and mitochondrial function is of increasing interest. Studies looking for such interactions are usually made in muscle and only a few studies have been done in liver, which is known to be a crucial partner in whole body insulin action. Recent studies have revealed a similar mechanism to that of muscle for fat-induced insulin resistance in liver. However, the exact mechanism of lipid metabolites accumulation in liver leading to insulin resistance is far from being elucidated. One of the hypothetical mechanisms for liver steatosis development is an impairment of mitochondrial function. We examined mitochondrial function in fatty liver and insulin resistance state using isolated mitochondria from obese Zucker rats. We determined the relationship between ATP synthesis and oxygen consumption as well as the relationship between mitochondrial membrane potential and oxygen consumption. In order to evaluate the quantity of mitochondria and the oxidative capacity we measured citrate synthase and cytochrome c oxidase activities. Results showed that despite significant fatty liver and hyperinsulinemia, isolated liver mitochondria from obese Zucker rats display no difference in oxygen consumption, ATP synthesis, and membrane potential compared with lean Zucker rats. There was no difference in citrate synthase and cytochrome c oxidase activities between obese and lean Zucker rats in isolated mitochondria as well as in liver homogenate, indicating a similar relative amount of hepatic mitochondria and a similar oxidative capacity. Adiponectin, which is involved in bioenergetic homeostasis, was increased two-fold in obese Zucker rats despite insulin resistance. In conclusion, isolated liver mitochondria from lean and obese insulin-resistant Zucker rats showed strictly the same mitochondrial function. It remains to be elucidated whether adiponectin increase is involved in these results.
胰岛素抵抗与线粒体功能之间的关系日益受到关注。探寻此类相互作用的研究通常在肌肉中进行，而在肝脏中开展的研究较少，尽管肝脏是全身胰岛素作用的关键参与者。近期研究揭示，肝脏中脂肪诱导的胰岛素抵抗机制与肌肉中的类似。然而，肝脏中脂质代谢产物蓄积导致胰岛素抵抗的确切机制仍远未阐明。肝脂肪变性发展的一种假说机制是线粒体功能受损。我们使用肥胖Zucker大鼠分离出的线粒体，研究了脂肪肝和胰岛素抵抗状态下的线粒体功能。我们测定了ATP合成与氧气消耗之间的关系以及线粒体膜电位与氧气消耗之间的关系。为了评估线粒体数量和氧化能力，我们测量了柠檬酸合酶和细胞色素c氧化酶的活性。结果显示，尽管存在明显的脂肪肝和高胰岛素血症，但与瘦Zucker大鼠相比，肥胖Zucker大鼠分离出的肝脏线粒体在氧气消耗、ATP合成和膜电位方面并无差异。在分离出的线粒体以及肝脏匀浆中，肥胖和瘦Zucker大鼠的柠檬酸合酶和细胞色素c氧化酶活性并无差异，这表明肝脏线粒体的相对数量相似且氧化能力相似。尽管存在胰岛素抵抗，但参与生物能量稳态的脂联素在肥胖Zucker大鼠中增加了两倍。总之，来自瘦和肥胖胰岛素抵抗Zucker大鼠的分离肝脏线粒体显示出完全相同的线粒体功能。脂联素增加是否与这些结果有关仍有待阐明。
