Mitochondrial and performance adaptations to exercise training in mice lacking skeletal muscle LKB1
Mitochondrial and performance adaptations to exercise training in mice lacking skeletal muscle LKB1
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DOI：
10.1152/ajpendo.00227.2013
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发表时间：
2013-10-01
影响因子：
5.1
通讯作者：
Thomson, David M.
中科院分区：
文献类型：
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作者：
Tanner, Colby B.;Madsen, Steven R.;Thomson, David M.
LKB 1及其AMP活化蛋白激酶家族的下游靶点是骨骼肌细胞功能许多方面的重要调节剂，包括线粒体含量和毛细作用的控制。骨骼肌和心肌中的LKB 1缺陷（mLKB 1-KO）极大地损害运动能力。然而，该遗传模型中的心功能障碍阻碍了对骨骼肌LKB 1在观察到的效应中的作用的明确评估。我们的目的是确定骨骼肌特异性敲除LKB 1（skmLKB 1-KO）是否会降低运动能力和线粒体蛋白含量，损害运动训练后线粒体蛋白的积累，并减弱运动训练后跑步成绩的改善。我们发现，与对照组（CON）小鼠相比，skmLKB 1-KO小鼠的跑步机和自主轮跑步能力降低。柠檬酸合酶活性，琥珀酸脱氢酶活性，丙酮酸脱氢酶激酶含量较低KO与CON肌肉。三周的跑步机训练导致CON和skmLKB 1-KO小鼠的跑步机跑步表现显著增加。柠檬酸合酶活性显着增加，在这两种基因型的训练，但蛋白质含量和活性的线粒体电子传递链的组件增加，只有在CON小鼠。与CON肌肉相比，skmLKB 1-KO中的毛细血管和VEGF蛋白较低，但VEGF仅在skmLKB 1-KO中随着训练而增加。急性肌肉收缩3小时后，CON中的PGC-1 α、细胞色素c和VEGF基因表达均增加，但skmLKB 1-KO肌肉没有增加。我们的研究结果表明，骨骼肌LKB 1是所需的一些线粒体蛋白的增生，但不是早期运动能力的提高与运动训练。
LKB1 and its downstream targets of the AMP-activated protein kinase family are important regulators of many aspects of skeletal muscle cell function, including control of mitochondrial content and capillarity. LKB1 deficiency in skeletal and cardiac muscle (mLKB1-KO) greatly impairs exercise capacity. However, cardiac dysfunction in that genetic model prevents a clear assessment of the role of skeletal muscle LKB1 in the observed effects. Our purposes here were to determine whether skeletal muscle-specific knockout of LKB1 (skmLKB1-KO) decreases exercise capacity and mitochondrial protein content, impairs accretion of mitochondrial proteins after exercise training, and attenuates improvement in running performance after exercise training. We found that treadmill and voluntary wheel running capacity was reduced in skmLKB1-KO vs. control (CON) mice. Citrate synthase activity, succinate dehydrogenase activity, and pyruvate dehydrogenase kinase content were lower in KO vs. CON muscles. Three weeks of treadmill training resulted in significantly increased treadmill running performance in both CON and skmLKB1-KO mice. Citrate synthase activity increased significantly with training in both genotypes, but protein content and activity for components of the mitochondrial electron transport chain increased only in CON mice. Capillarity and VEGF protein was lower in skmLKB1-KO vs. CON muscles, but VEGF increased with training only in skmLKB1-KO. Three hours after an acute bout of muscle contractions, PGC-1 alpha, cytochrome c, and VEGF gene expression all increased in CON but not skmLKB1-KO muscles. Our findings indicate that skeletal muscle LKB1 is required for accretion of some mitochondrial proteins but not for early exercise capacity improvements with exercise training.