BACKGROUND Physical inactivity contributes to muscle wasting and reductions in mitochondrial oxidative phenotype (OXPHEN), reducing physical performance and quality of life during aging and in chronic disease. Previously, it was shown that inactivation of glycogen synthase kinase (GSK)-3β stimulates muscle protein accretion, myogenesis, and mitochondrial biogenesis. Additionally, GSK-3β is inactivated during recovery of disuse-induced muscle atrophy. AIM Therefore, we hypothesize that GSK-3 inhibition is required for reloading-induced recovery of skeletal muscle mass and OXPHEN. METHODS Wild-type (WT) and whole-body constitutively active (C.A.) Ser21/9 GSK-3α/β knock-in mice were subjected to a 14-day hind-limb suspension/14-day reloading protocol. Soleus muscle mass, fiber cross-sectional area (CSA), OXPHEN (abundance of sub-units of oxidative phosphorylation (OXPHOS) complexes and fiber-type composition), as well as expression levels of their main regulators (respectively protein synthesis/degradation, myogenesis and peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) signaling) were monitored. RESULTS Subtle but consistent differences suggesting suppression of protein turnover signaling and decreased expression of several OXPHOS sub-units and PGC-1α signaling constituents were observed at baseline in C.A. GSK-3 versus WT mice. Although soleus mass recovery during reloading occurred more rapidly in C.A. GSK-3 mice, this was not accompanied by a parallel increased CSA. The OXPHEN response to reloading was not distinct between C.A. GSK-3 and WT mice. No consistent or significant differences in reloading-induced changes in the regulatory steps of protein turnover, myogenesis or muscle OXPHEN were observed in C.A. GSK-3 compared to WT muscle. CONCLUSION This study indicates that GSK-3 inactivation is dispensable for reloading-induced recovery of muscle mass and OXPHEN.

中文翻译：

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停用后恢复肌肉质量和肌肉氧化表型不需要GSK-3失活。

背景技术缺乏运动会导致肌肉消瘦并减少线粒体氧化表型（OXPHEN），从而降低衰老和慢性疾病期间的身体机能和生活质量。以前，已经证明糖原合酶激酶（GSK）-3β的失活会刺激肌肉蛋白的积聚，肌生成和线粒体生物生成。另外，在废用诱导的肌肉萎缩的恢复过程中，GSK-3β被灭活。目的因此，我们假设GSK-3抑制是重载诱导的骨骼肌质量和OXPHEN的恢复所必需的。方法对野生型（WT）和全身组成型活性（CA）Ser21 / 9GSK-3α/β敲入小鼠进行14天后肢悬吊/ 14天重载实验。比目鱼肌质量，纤维截面积（CSA），OXPHEN（氧化磷酸化（OXPHOS）复合物的亚基的丰富和纤维类型的组成）及其主要调节因子的表达水平（分别是蛋白质的合成/降解，肌发生和过氧化物酶体增殖物激活的受体-γ共激活子-监测1α（PGC-1α）信号）。结果在CA GSK-3和WT小鼠的基线观察到微妙但一致的差异，提示其抑制了蛋白质更新信号，并抑制了几种OXPHOS亚基和PGC-1α信号成分的表达。尽管在CA GSK-3小鼠中重载时的比目鱼肿块恢复更快，但并没有同时增加CSA。OXPHEN对重载的反应在CA GSK-3和WT小鼠之间并不明显。与野生型肌肉相比，在CA GSK-3中未观察到重载诱导的蛋白质更新，肌生成或肌肉OXPHEN调控步骤的变化一致或显着差异。结论这项研究表明，GSK-3失活对于重装诱导的肌肉质量和OXPHEN的恢复是必不可少的。