Tissue taurine depletion alters metabolic response to exercise and reduces running capacity in mice.
Tissue taurine depletion alters metabolic response to exercise and reduces running capacity in mice.
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DOI：
10.1155/2014/964680
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Azuma J
中科院分区：
文献类型：
--
作者：
Ito T;Yoshikawa N;Schaffer SW;Azuma J
牛磺酸是一种含硫氨基酸，在骨骼肌中的浓度非常高。通过敲除牛磺酸转运蛋白基因而改造的牛磺酸缺陷小鼠表现出骨骼肌萎缩、结构缺陷和运动耐受不良。在本研究中，我们研究了TauTKO表型的肌肉中代谢异常和运动不耐受的发展机制。TauTKO小鼠的跑步速度和耐力时间低于对照小鼠。在TauTKO小鼠中，在跑步机跑步期间，血液乳酸水平升高>3倍，但在WT小鼠中，运动基本上保持不变。TauTKO小鼠在跑步机跑步期间血糖清除速度比WT小鼠快。在TauTKO肌肉中，AMPK β-2亚基减少，同时AMPK α1和α2亚基减少。在TauTKO肌肉中，PPARα及其靶点Gpx 3、Cpt 2和Echs 1的水平也降低。总的来说，牛磺酸耗竭损害骨骼肌对运动的代谢适应，这是一种与AMPK下调和线粒体呼吸链对NADH利用减少相关的现象。这些研究结果表明，牛磺酸在调节运动TauTKO小鼠骨骼肌能量代谢中起着至关重要的作用，这些变化导致运动耐力受损。
Taurine is a sulfur-containing amino acid found in very high concentration in skeletal muscle. Taurine deficient mice engineered by knocking out the taurine transporter gene exhibit skeletal muscle wasting, structural defects, and exercise intolerance. In the present study, we investigated the mechanism underlying the development of metabolic abnormalities and exercise intolerance in muscle of the TauTKO phenotype. Running speed and endurance time of TauTKO mice were lower than those of control mice. Blood lactate level was elevated by >3-fold during treadmill running in TauTKO mice but remained largely unaltered by exercise in WT mice. Blood glucose was cleared faster during treadmill running in TauTKO mice than WT mice. AMP-activated kinase (AMPK) β-2 subunit was reduced in TauTKO muscle concomitant with a reduction in α1 and α2 subunits of AMPK. The level of PPARα and its targets, Gpx3, Cpt2, and Echs1, were also decreased in TauTKO muscle. Collectively, taurine depletion impairs metabolic adaptation to exercise in skeletal muscle, a phenomenon associated with a downregulation of AMPK and diminished NADH utilization by the mitochondrial respiratory chain. These findings suggest a crucial role of taurine in regulating energy metabolism in skeletal muscle of exercising TauTKO mice, changes that contribute to impaired exercise endurance.