Loaded wheel running and muscle adaptation in the mouse

John P. Konhilas, Ulrika Widegren, David L. Allen, Angelika C. Paul, Allison Cleary, Leslie A. Leinwand

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


Voluntary cage wheel exercise has been used extensively to determine the physiological adaptation of cardiac and skeletal muscle in mice. In this study, we tested the effect of different loading conditions on voluntary cage wheel performance and muscle adaptation. Male C57B1/6 mice were exposed to a cage wheel with no-resistance (NR), low-resistance (LR), or high-resistance (HR) loads for 7 wk. Power output was elevated (3-fold) under increased loading (LR and HR) conditions compared with unloaded (NR) exercise training. Only unloaded (NR) exercise induced an increase in heart mass, whereas only loaded (LR and HR) exercise training 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 pathological (but not physiological) cardiac hypertrophy and a decrease in calcineurin expression in all exercise groups. In addition, transcriptional activity of myocyte enhancer factor-2 (MEF-2) was significantly decreased in the hearts of the LR group as determined by a MEF-2-dependent transgene driving the expression of β-galactosidase. Phosphorylation of glycogen synthase kinase-3β, protein kinase B (Akt), and p70 S6 kinase 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.

Original languageEnglish (US)
Pages (from-to)H455-H465
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1 58-1
StatePublished - Jul 2005


  • Cardiac adaptation
  • Cardiomyocyte signaling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


Dive into the research topics of 'Loaded wheel running and muscle adaptation in the mouse'. Together they form a unique fingerprint.

Cite this