Rovira Mireia, Arrey Gerard, Planas Josep V
Departament de Biologia Cel·lular, Facultat de Biologia, Fisiologia i Immunologia, Universitat de Barcelona, Barcelona, Spain.
Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain.
Front Physiol. 2017 Dec 18;8:1063. doi: 10.3389/fphys.2017.01063. eCollection 2017.
Skeletal muscle is a plastic tissue that undergoes cellular and metabolic adaptations under conditions of increased contractile activity such as exercise. Using adult zebrafish as an exercise model, we previously demonstrated that swimming training stimulates hypertrophy and vascularization of fast muscle fibers, consistent with the known muscle growth-promoting effects of exercise and with the resulting increased aerobic capacity of this tissue. Here we investigated the potential involvement of factors and signaling mechanisms that could be responsible for exercise-induced fast muscle remodeling in adult zebrafish. By subjecting zebrafish to swimming-induced exercise, we observed an increase in the activity of mammalian target of rapamycin (mTOR) and Mef2 protein levels in fast muscle. We also observed an increase in the protein levels of the mitotic marker phosphorylated histone H3 that correlated with an increase in the protein expression levels of Pax7, a satellite-like cell marker. Furthermore, the activity of AMP-activated protein kinase (AMPK) was also increased by exercise, in parallel with an increase in the mRNA expression levels of α and also of , a β-oxidation marker. Changes in the mRNA expression levels of slow and fast myosin markers further supported the notion of an exercise-induced aerobic phenotype in zebrafish fast muscle. The mRNA expression levels of and and , myokines known in mammals to be produced in response to exercise and to signal through mTOR/AMPK pathways, among others, were increased in fast muscle of exercised zebrafish. These results support the notion that exercise increases skeletal muscle growth and myogenesis in adult zebrafish through the coordinated activation of the mTOR-MEF2 and AMPK-PGC1α signaling pathways. These results, coupled with altered expression of markers for oxidative metabolism and fast-to-slow fiber-type switch, also suggest improved aerobic capacity as a result of swimming-induced exercise. Finally, the induction of myokine expression by swimming-induced exercise support the hypothesis that these myokines may have been produced and secreted by the exercised zebrafish muscle and acted on fast muscle cells to promote metabolic remodeling. These results support the use of zebrafish as a suitable model for studies on muscle remodeling in vertebrates, including humans.
骨骼肌是一种可塑性组织，在诸如运动等收缩活动增加的情况下会经历细胞和代谢适应性变化。我们之前以成年斑马鱼作为运动模型，证明游泳训练会刺激快肌纤维的肥大和血管生成，这与运动促进肌肉生长的已知效应以及该组织由此增加的有氧能力相一致。在这里，我们研究了可能导致成年斑马鱼运动诱导的快肌重塑的因素和信号传导机制。通过使斑马鱼进行游泳诱导的运动，我们观察到快肌中雷帕霉素靶蛋白（mTOR）的活性和Mef2蛋白水平增加。我们还观察到有丝分裂标记物磷酸化组蛋白H3的蛋白水平增加，这与卫星样细胞标记物Pax7的蛋白表达水平增加相关。此外，运动还使AMP激活的蛋白激酶（AMPK）的活性增加，同时α以及β氧化标记物的mRNA表达水平也增加。慢肌球蛋白和快肌球蛋白标记物的mRNA表达水平变化进一步支持了斑马鱼快肌存在运动诱导的有氧表型这一观点。在运动斑马鱼的快肌中，哺乳动物中已知因运动而产生并通过mTOR/AMPK等途径发出信号的肌动蛋白和鸢尾素的mRNA表达水平增加。这些结果支持这样一种观点，即运动通过mTOR - MEF2和AMPK - PGC1α信号通路的协同激活，增加成年斑马鱼的骨骼肌生长和肌生成。这些结果，再加上氧化代谢标记物和快肌纤维类型向慢肌纤维类型转变的表达改变，也表明游泳诱导的运动提高了有氧能力。最后，游泳诱导的运动对肌动蛋白表达的诱导支持了这样一种假说，即这些肌动蛋白可能由运动的斑马鱼肌肉产生并分泌，作用于快肌细胞以促进代谢重塑。这些结果支持将斑马鱼作为研究包括人类在内的脊椎动物肌肉重塑的合适模型。
