Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
PLoS One. 2010 Oct 22;5(10):e13535. doi: 10.1371/journal.pone.0013535.
Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle.
虽然骨骼肌代谢是一个研究得很好的生理过程，但对于它在转录水平上是如何被调节的知之甚少。成肌转录因子肌生成素在胚胎和胎儿期的骨骼肌发育中是必需的，但肌生成素在成年骨骼肌中的作用尚不清楚。我们试图确定肌生成素在成年肌肉代谢中的功能。使用 Myog 条件性等位基因和 Cre-ER 转基因在成年小鼠中删除 Myog。通过非自愿跑步机跑步来分析小鼠的运动能力。为了评估氧化和糖酵解代谢，我们进行了间接测热法、监测血糖和乳酸水平，并对肌肉纤维进行了组织化学分析。令人惊讶的是，我们发现 Myog 缺失的小鼠在高强度和低强度跑步机跑步中的表现明显优于对照组。这种增强的运动能力是由于在低强度和高强度运动中氧化代谢更有效，以及在高强度运动中糖酵解代谢更有效。此外，Myog 缺失的小鼠对长期自愿跑步轮训练的反应增强。我们确定了几个候选基因，它们在缺乏肌生成素的运动应激肌肉中的表达发生了改变。结果表明，肌生成素作为一个高级转录调节剂，在控制成年骨骼肌中有氧和无氧代谢之间的能量平衡方面起着关键作用。
