Abstract
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 pgc1α and also of pparda, 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 il6, il6r, apln, aplnra and aplnrb, sparc, decorin and igf1, 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.
Highlights
In vertebrates, skeletal muscle is a plastic and dynamic tissue that can be remodeled in response to different stimuli, such as exercise or physical activity, and that contributes to maintain metabolic homeostasis
Aerobic exercise conditions, we reported that swimming-induced exercise stimulated somatic growth and increased hypertrophy and capillarization of fast skeletal muscle fibers that was accompanied by the activation of transcriptional programs involved in muscle growth, myogenesis, oxidative metabolism and angiogenic processes (Palstra et al, 2010, 2014)
The activity of 4EBP-1, higher in exercised over non-exercised zebrafish, was not significantly different (P = 0.066) between the two groups (Figure 1B). These results suggest that an activation of the mammalian target of rapamycin (mTOR) pathway and an increase in Mef2 content in fast skeletal muscle were induced by swimming training in adult zebrafish, supporting the notion that exercise stimulates skeletal muscle growth in adult zebrafish through a mTOR-dependent pathway
Summary
Skeletal muscle is a plastic and dynamic tissue that can be remodeled in response to different stimuli, such as exercise or physical activity, and that contributes to maintain metabolic homeostasis. The mammalian target of rapamycin complex (mTORC), which integrates many intracellular signals in order to regulate anabolic processes, cell cycle progression and autophagy, is suggested to be the main signaling pathway enhancing protein synthesis and to promote skeletal muscle fiber hypertrophy in response to exercise in mammals (Laplante and Sabatini, 2012; Egan and Zierath, 2013; Hawley et al, 2014). Exercised skeletal muscle develops an increased aerobic capacity that has been associated with elevated mitochondrial biogenesis and oxidative metabolism, changes in muscle fiber type or increased oxygen availability as a result of increased muscle capillarization (Egan and Zierath, 2013; Hawley et al, 2014). AMPK is activated in response to muscle contraction or endurance exercise (Winder and Hardie, 1996; Narkar et al, 2008; Nedachi et al, 2008) in an intensity- and duration-dependent manner (Bergeron et al, 2001; Egan et al, 2010)
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