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1 Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, CO, USA
* To whom correspondence should be addressed. E-mail: Leslie.Leinwand{at}colorado.edu.
Voluntary cage wheel exercise has been used extensively to determine the physiological adaptation of cardiac and skeletal muscle in mice. In this study, we have tested the effect of different loading conditions on voluntary cage wheel performance and muscle adaptation. Male C57/Bl6 mice were exposed to a cage wheel with no resistance (NR), low resistance (LR), or high resistance (HR) loads for 7 weeks. Power output was elevated (3-fold) under increased loading (LR and HR) conditions compared to unloaded (NR) exercise training. Only unloaded exercise (NR) induced an increase in heart mass, whereas only loaded exercise training (LR and HR) induced an increase in skeletal (soleus) muscle mass. Moreover, unloaded and loaded exercise training had a differential impact on the cross-sectional area of muscle fibers depending on the type of myosin heavy chain expressed by each fiber. The biochemical adaptation of the heart was characterized by a decrease in genes associated with pathologic (but not physiologic) cardiac hypertrophy and a decrease in calcineurin expression in all exercise groups. In addition, transcriptional activity of myocyte enhancer factor 2 (MEF2) was significantly decreased in the hearts of the LR group as determined by a MEF2-dependent transgene driving the expression of B-galactosidase. Phosphorylation of glycogen-synthase kinase-3B (GSK-3B), protein kinase B (Akt), and p70S6-kinase (p70S6k) was increased only in the hearts of the NR group, consistent with the significant increase in cardiac mass. In conclusion, unloaded and loaded cage wheel exercise have a differential impact on cage wheel performance and muscle (cardiac and skeletal) adaptation.
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