Franchi Martino V, Candia Julián, Sarto Fabio, Sirago Giuseppe, Valli Giacomo, Paganini Matteo, Hartnell Lisa, Giacomello Emiliana, Toniolo Luana, Monti Elena, Nogara Leonardo, Moro Tatiana, Paoli Antonio, Murgia Marta, Brocca Lorenza, Pellegrino Maria Antonietta, Grassi Bruno, Bottinelli Roberto, De Vito Giuseppe, Ferrucci Luigi, Narici Marco V
Department of Biomedical Sciences, University of Padova, Padova, Italy.
CIR-MYO Myology Center, University of Padova, Padova, Italy.
J Physiol. 2025 Jul;603(13):3725-3753. doi: 10.1113/JP287003. Epub 2025 Jan 10.
Short-term unloading experienced following injury or hospitalisation induces muscle atrophy and weakness. The effects of exercise following unloading have been scarcely investigated. We investigated the functional and molecular adaptations to a resistance training (RT) programme following short-term unloading. Eleven males (22.09 ± 2.91 years) underwent 10 days of unilateral lower limb suspension (ULLS) followed by 21 days of knee extensor RT (three times/week). Data collection occurred at Baseline (LS0), after ULLS (LS10) and at active recovery (AR21). Knee extensor maximum voluntary contraction (MVC) was evaluated. Quadriceps volume was estimated by ultrasonography. Muscle fibre cross-sectional area, fibre type distribution, glycogen content and succinate dehydrogenase (SDH) activity were measured from vastus lateralis biopsies. Mitochondrial-related proteins were quantified by western blot and transcriptional responses were assessed by RNA sequencing. Following ULLS, quadriceps volume and MVC decreased significantly (3.7%, P < 0.05; 29.3%, P < 0.001). At AR21 (vs. LS10), MVC was fully restored (42%) and quadriceps volume increased markedly (18.6%, P < 0.001). Glycogen content and whole-body water increased at AR21 (14%, P < 0.001; 3.1%, P < 0.05). We observed a marked increase in fibre type I at AR21 (38%, P < 0.05). SDH immunoreactivity increased significantly after exercise (20%, P < 0.001). Mitochondrial fusion (MFN1, MFN2 and OPA1) and fission (DRP1) proteins were markedly increased by RT, and the most differentially expressed genes belonged to oxidative phosphorylation pathways. In contrast with what is usually observed after RT, oxidative metabolism, slow fibre type and mitochondrial dynamics were enhanced beyond expected. We propose that prior exposure to short-term muscle unloading may drive the nature of molecular adaptations to subsequent RT. KEY POINTS: Short-term unloading is often experienced during recovery from injuries and hospitalisation, leading to loss of muscle mass and strength. Although exercise can be beneficial in mitigating/reversing such alterations during disuse, only a few studies have focused on the effects of exercise following muscle unloading. With an integrative physiological approach, we aimed to elucidate the basic mechanisms of muscle function recovery in response to 21 days of resistance exercise that followed 10 days of unilateral lower limb suspension (ULLS), assessing whether the mechanisms underlying recovery are defined by a specific reversal of those that occurred during disuse. Resistance training was successful in recovering functional and structural muscle properties after 10 days of ULLS, but in contrast with what is usually observed in response to this training modality, oxidative metabolism and slow fibre type were mostly enhanced. We propose that prior exposure to short-term muscle unloading may drive the adaptations to subsequent exercise.
受伤或住院后经历的短期肢体失用会导致肌肉萎缩和无力。关于肢体失用后运动的影响，鲜有研究涉及。我们研究了短期肢体失用后进行抗阻训练（RT）计划时的功能和分子适应性变化。11名男性（22.09±2.91岁）经历了10天的单侧下肢悬吊（ULLS），随后进行21天的伸膝抗阻训练（每周3次）。在基线期（LS0）、ULLS后（LS10）和主动恢复阶段（AR21）进行数据收集。评估伸膝最大自主收缩（MVC）。通过超声估计股四头肌体积。从外侧股四头肌活检样本中测量肌纤维横截面积、纤维类型分布、糖原含量和琥珀酸脱氢酶（SDH）活性。通过蛋白质免疫印迹法对线粒体相关蛋白进行定量，并通过RNA测序评估转录反应。ULLS后，股四头肌体积和MVC显著下降（分别为3.7%，P<0.05；29.3%，P<0.001）。在AR21（与LS10相比）时，MVC完全恢复（42%），股四头肌体积显著增加（18.6%，P<0.001）。AR21时糖原含量和全身水分增加（分别为14%，P<0.001；3.1%，P<0.05）。我们观察到AR21时I型纤维显著增加（38%，P<0.05）。运动后SDH免疫反应性显著增加（20%，P<0.001）。抗阻训练使线粒体融合（MFN1、MFN2和OPA1）和裂变（DRP1）蛋白显著增加，差异表达最明显的基因属于氧化磷酸化途径。与通常在抗阻训练后观察到的情况相反，氧化代谢、慢肌纤维类型和线粒体动力学的增强超出预期。我们认为，先前经历的短期肌肉失用可能会驱动对后续抗阻训练的分子适应性变化。要点：在受伤恢复和住院期间经常会经历短期肢体失用，导致肌肉质量和力量丧失。尽管运动有助于减轻/逆转废用期间的此类变化，但只有少数研究关注肌肉失用后运动的影响。通过综合生理学方法，我们旨在阐明在10天单侧下肢悬吊（ULLS）后进行21天抗阻运动时肌肉功能恢复的基本机制，评估恢复的机制是否由废用期间发生的特定逆转所定义。抗阻训练成功地在ULLS 10天后恢复了肌肉的功能和结构特性，但与通常对这种训练方式的反应相反，氧化代谢和慢肌纤维类型大多得到增强。我们认为，先前经历短期肌肉失用可能会驱动对后续运动的适应性变化。
