Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen , Copenhagen , Denmark.
Section of Integrated Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen , Copenhagen , Denmark.
Am J Physiol Endocrinol Metab. 2018 Jan 1;314(1):E1-E20. doi: 10.1152/ajpendo.00082.2017. Epub 2017 Sep 5.
PGC-1α has been suggested to regulate exercise training-induced metabolic adaptations and autophagy in skeletal muscle. The factors regulating PGC-1α, however, have not been fully resolved. The aim was to investigate the impact of β-adrenergic signaling in PGC-1α-mediated metabolic adaptations in skeletal muscle with exercise training. Muscle was obtained from muscle-specific PGC-1α knockout (MKO) and lox/lox mice 1) 3 h after a single exercise bout with or without prior injection of propranolol or 3 h after a single injection of clenbuterol and 2) after 5 wk of wheel running exercise training with or without propranolol treatment or after 5 wk of clenbuterol treatment. A single clenbuterol injection and an acute exercise bout similarly increased the mRNA content of both N-terminal and full-length PGC-1α isoforms, and prior propranolol treatment reduced the exercise-induced increase in mRNA of all isoforms. Furthermore, a single clenbuterol injection elicited a PGC-1α-dependent increase in cytochrome c and vascular endothelial growth factor mRNA, whereas prolonged clenbuterol treatment increased fiber size but reduced capillary density. Exercise training increased the protein content of OXPHOS, LC3I, and Parkin in a PGC-1α-dependent manner without effect of propranolol, while an exercise training-induced increase in Akt2 and p62 protein required PGC-1α and was blunted by prolonged propranolol treatment. This suggests that β-adrenergic signaling is not required for PGC-1α-mediated exercise training-induced adaptations in mitochondrial proteins, but contributes to exercise training-mediated adaptations in insulin signaling and autophagy regulation through PGC-1α. Furthermore, changes observed with acute stimulation of compounds like clenbuterol and propranolol may not lead to corresponding adaptations with prolonged treatment.
PGC-1α 被认为可以调节运动训练引起的骨骼肌代谢适应和自噬。然而，调节 PGC-1α 的因素尚未完全解决。本研究旨在探讨β-肾上腺素能信号在运动训练引起的 PGC-1α 介导的代谢适应中的作用。从肌肉特异性 PGC-1α 敲除（MKO）和 lox/lox 小鼠中获取肌肉，1）在单次运动后 3 小时，有无事先注射普萘洛尔，或在单次注射克仑特罗后 3 小时，2）在 5 周的轮跑运动训练后，有无普萘洛尔治疗，或在 5 周的克仑特罗治疗后。单次克仑特罗注射和急性运动同样增加了 N 端和全长 PGC-1α 同工型的 mRNA 含量，而预先给予普萘洛尔处理则降低了运动诱导的所有同工型的 mRNA 增加。此外，单次克仑特罗注射引起 PGC-1α 依赖性的细胞色素 c 和血管内皮生长因子 mRNA 的增加，而长期克仑特罗处理增加了纤维大小，但降低了毛细血管密度。运动训练以 PGC-1α 依赖的方式增加了 OXPHOS、LC3I 和 Parkin 的蛋白含量，而普萘洛尔没有影响，而运动训练诱导的 Akt2 和 p62 蛋白的增加需要 PGC-1α，并被长期普萘洛尔处理所抑制。这表明β-肾上腺素能信号不是 PGC-1α 介导的运动训练诱导的线粒体蛋白适应所必需的，但通过 PGC-1α 促进了胰岛素信号和自噬调节的适应。此外，急性刺激化合物（如克仑特罗和普萘洛尔）引起的变化可能不会导致长期治疗时出现相应的适应。
