Low responders to endurance training exhibit impaired hypertrophy and divergent biological process responses in skeletal muscle

Divergent skeletal muscle phenotypes result from chronic resistance-type- versus endurance-type contraction, reflecting the principle of training specificity. However, it is unclear whether there is a common set of genetic factors that influence skeletal muscle adaptation to different modes of training. Female rats were obtained from out-bred lines selectively bred from high responders to endurance training (HRT) or low responders to endurance training (LRT; n=6/group; generation 19). Both groups underwent 14 d of synergist ablation to induce functional overload of the plantaris muscle prior to comparison to non-overload controls of the same genotype. RNA sequencing was performed to identify Gene Ontology Biological Processes with differential (LRT vs HRT) gene set enrichment. Running distance, determined well in advance of synergist ablation, increased in response to aerobic training in HRT but not LRT (65 ±26% versus -6 ±18%, respectively, mean ±SD, p<0.0001). The hypertrophy response to functional overload was attenuated in LRT versus HRT (20.1 ±5.6% versus 41.6 ±16.1%, respectively, P = 0.015). There were between-group differences in the magnitude of response of 96 upregulated- and 101 downregulated pathways. A further 27 pathways showed contrasting upregulation or downregulation in LRT versus HRT in response to functional overload. In conclusion, low responders to aerobic endurance training were also low responders for compensatory hypertrophy, and attenuated hypertrophy was associated with differential gene expression. Thus, our findings suggest that genetic factors that underpin aerobic training maladaptation may also dysregulate the transcriptional activity of biological processes that contribute to adaptation to mechanical overload.慢性抗阻收缩与耐力收缩可引发截然不同的骨骼肌表型，这契合了训练特异性原则。然而目前尚不清楚，是否存在一组共同的遗传因子，可调控骨骼肌对不同训练模式的适应性重塑。本研究使用的雌性大鼠来自针对耐力训练高反应者（High Responders to Endurance Training, HRT）与耐力训练低反应者（Low Responders to Endurance Training, LRT）选育的远交种群，每组样本量为6，处于第19代繁育。两组大鼠均接受14天的协同肌切除术，以诱发跖肌（plantaris muscle）功能性超负荷，并与同基因型的非超负荷对照组开展对比实验。本研究通过RNA测序（RNA sequencing），筛选出两组间（LRT vs HRT）基因集富集存在差异的基因本体生物学过程（Gene Ontology Biological Processes, GO-BP）。在协同肌切除术术前许久已测定的跑步距离显示，有氧训练可使HRT组大鼠的跑步距离提升（65±26%），但LRT组无显著变化（-6±18%，平均值±标准差，p<0.0001）。LRT组大鼠对功能性超负荷的肌肥大反应较HRT组减弱，分别为20.1±5.6%与41.6±16.1%（P=0.015）。两组间共有96条上调通路与101条下调通路的响应幅度存在显著差异。另有27条通路在两组对功能性超负荷的响应中呈现出相反的上调/下调趋势。综上，有氧耐力训练低反应者同时也是代偿性肌肥大的低反应者，而肌肥大反应减弱与基因表达差异密切相关。本研究结果表明，介导有氧训练适应性不良的遗传因子，或许同样会紊乱参与机械超负荷适应性重塑的生物学过程的转录活性。