title: Loaded wheel running and muscle adaptation in the mouse.
abstract: 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 C57Bl/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 beta-galactosidase. Phosphorylation of glycogen synthase kinase-3beta, 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.
authors.affiliation: Dept. of Molecular, Cellular, and Developmental Biology, Univ. of Colorado, Campus Box 347, Boulder, CO 80309-0347, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Konhilas
authors.forename: Ulrika
authors.initials: U
authors.lastname: Widegren
authors.forename: David L
authors.initials: DL
authors.lastname: Allen
authors.forename: Angelika C
authors.initials: AC
authors.lastname: Paul
authors.forename: Allison
authors.initials: A
authors.lastname: Cleary
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Leinwand
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006321:Heart / Q000502:physiology; D064326:MEF2 Transcription Factors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D018006:Myogenic Regulatory Factors; D010766:Phosphorylation; D005082:Physical Exertion / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D038362:Glycogen Synthase Kinase 3; D019703:Calcineurin