Progressive resistance-loaded voluntary wheel running increases hypertrophy and differentially affects muscle protein synthesis, ribosome biogenesis, and proteolytic markers in rat muscle

We examined if 6 weeks of progressive resistance-loaded voluntary wheel running in rats induced plantaris, soleus, and/or gastrocnemius hypertrophy and/or affected markers of translational efficiency, ribosome biogenesis, and markers of proteolysis. For 6 weeks, 8 male Sprague-Dawley rats (~9–10 weeks of age, ~300–325 g) rats were assigned to the progressive resistance-loaded voluntary wheel running model (EX), and ten rats were not trained (SED). For EX rats, the wheel-loading paradigm was as follows – days 1–7: free-wheel resistance, days 8–15: wheel resistance set to 20%–25% body mass, days 16–24: 40% body mass, days 25–32: 60% body mass, days 33–42: 40% body mass. Following the intervention, muscles were analysed for markers of translational efficiency, ribosome biogenesis, and muscle proteolysis. Raw gastrocnemius mass (+13%, p <.01), relative (body mass-corrected) gastrocnemius mass (+16%, p <.001), raw plantaris mass (+13%, p <.05), and relative plantaris mass (+15%, p <.01) were greater in EX vs. SED rats. In spite of gastrocnemius hypertrophy, EX animals presented a 54% decrease in basal muscle protein synthesis levels (p <.01), a 125% increase in pan 4EBP1 levels (p <.001) and a 31% decrease in pan eIF4E levels (p <.05). However, in relation to SED animals, EX animals presented a 70% increase in gastrocnemius c-Myc protein levels (p <.05). Most markers of translational efficiency and ribosome biogenesis were not altered in the plantaris or soleus muscles of EX vs. SED animals. Gastrocnemius F-box protein 32 and poly-ubiquinated protein levels were approximately 150% and 200% greater in SED vs. EX rats (p <.001). These data suggest that the employed resistance training model increases hind limb muscle hypertrophy, and this may be mainly facilitated through reductions in skeletal muscle proteolysis, rather than alterations in ribosome biogenesis or translational efficiency.