Skeletal muscle effects of two different 10-week exercise regimens, voluntary wheel running, and forced treadmill running, in mice: A pilot study

Physical activity and exercise induce a complex pattern of adaptation reactions in a broad variety of tissues and organs, particularly the cardiovascular and the musculoskeletal systems. The underlying mechanisms, however, specifically the molecular changes that occur in response to training, are still incompletely understood. Animal models help to systematically elucidate the mechanisms of exercise adaptation. With regard to endurance-based running exercise in mice, two basic regimens have been established: forced treadmill running (FTR), usually consisting of several sessions per week, and voluntary wheel running (VWR). However, the effects of these two programs on skeletal muscle molecular adaptation patterns have never been directly compared. To address this issue, in a pilot study, we analyzed the effects of two ten-week training regimens in juvenile, male, C57BL/6 mice: moderate-intensity forced treadmill running three-times-a-week, employing a protocol that has been widely used in similar studies before, and voluntary wheel running. Our data suggest that there are similarities, but also characteristic differences in the molecular responses of different skeletal muscle species to the two training regimens. In particular, we found that VWR induces a significant fiber type shift toward more type IIX fibers in the slow, oxidative soleus muscle (p = .0053), but not in the other three muscles analyzed. In addition, while training-induced expression patterns of the two metabolic markers Ppargc1a, encoding Pgc-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) and Nr4a3 (nuclear receptor subfamily 4 group A member 3) were roughly similar, downregulation of the Mstn (myostatin) gene and the "atrogene" Fbox32 could only be observed in response to VWR in specific muscles, such as in the gastrocnemius (p = .0015 for Mstn) and in the tibialis anterior (p = .0053 for Fbox32) muscles, suggesting that molecular adaptation reactions to the two training regimens show distinct characteristics.