Abstract
Satellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling during exercise. Increased muscular activity stimulates SC accumulation and function, but to what extend alternations in mechanical load control SC fusion remains to be elucidated. To investigate SC contribution to myofibers during exercise training, we labeled SCs by excising tdTomato (mT) in Pax7CreERT2/+; Rosa26mTmG/+ mice, resulting in an mEGFP (mG) labeling of all PAX7+ cells and derived myofibers (Figure 1A). Using this genetic lineage tracing model, we here show that SCs extensively contribute to myofibers during exercise and that this occurs exclusively in hindlimb plantar flexors. Upon 8‐weeks of voluntary free running (VRun), 60% of all m. soleus myofibers had at least one SC fused (mG+). Moreover, adding load to the wheel (VResRun) increased the number of mG+ myofibers to 80%, indicating that SC fusion during exercise is load dependent (Figure 1B). Since only the VResRun showed substantial muscle hypertrophy in both m. soleus and m. plantaris, this data suggests that next to hypertrophy, also endurance‐training adaptions are mirrored by extensive SC fusion. Finally, exercise training induced a shift towards an oxidative fiber type, but SC fusion was similar in oxidative and glycolytic fibers. Collectively, we show that voluntary running strongly induces SC fusion in both free and resistance running conditions, but the latter only induced muscle hypertrophy. Thus, our findings suggest that SC fusion cannot only serve hypertrophy, since we also observed significant contribution under ‘endurance’ settings.Support or Funding InformationInternal funding ETH ZurichExercise induces satellite cell fusion in a load‐dependent manner. (A) mouse model and experimental protocol. (B) mG expression in mouse hindlimb muscle under sedentary (control) and running (VRun and VResRun) conditions. *** p<0.001, ** p<0.01.Figure 1
Highlights
Satellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling upon muscular contractions
By performing SC fate tracing experiments, we show that 8 weeks of voluntary wheel running increased SC contribution to myofibers in mouse plantar flexor muscles in a load-dependent, but fiber type-independent manner
Increased SC fusion was not exclusively linked to muscle hypertrophy as wheel running without external load substantially increased SC fusion in the absence of fiber hypertrophy
Summary
Satellite cells (SCs) are required for muscle repair following injury and are involved in muscle remodeling upon muscular contractions. No defects in intrinsic adaptations to endurance exercise (e.g., muscle vascularization, fiber type shift, or succinate dehydrogenase activity) were reported when SCs were ablated using the Pax7CreERT2-DTA model or Xray irridation, arguing against the necessity of SCs for adaptations to endurance exercise [16, 17]. It is currently unknown whether exercise training aimed to evoke endurance adaptions, but not muscle hypertrophy, stimulates SC contribution to myonuclei
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