title: Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice.
abstract: The importance of adequate levels of muscle size and function and physical activity is widely recognized. Myostatin/activin blocking increases skeletal muscle mass but may decrease muscle oxidative capacity and can thus be hypothesized to affect voluntary physical activity. Soluble activin receptor IIB (sActRIIB-Fc) was produced to block myostatin/activins. Modestly dystrophic mdx mice were injected with sActRIIB-Fc or PBS with or without voluntary wheel running exercise for 7 wk. Healthy mice served as controls. Running for 7 wk attenuated the sActRIIB-Fc-induced increase in body mass by decreasing fat mass. Running also enhanced/restored the markers of muscle oxidative capacity and autophagy in mdx mice to or above the levels of healthy mice. Voluntary running activity was decreased by sActRIIB-Fc during the first 3-4 wk correlating with increased body mass. Home cage physical activity of mice, quantified from the force plate signal, was decreased by sActRIIB-Fc the whole 7-wk treatment in sedentary mice. To understand what happens during the first weeks after sActRIIB-Fc administration, when mice are less active, healthy mice were injected with sActRIIB-Fc or PBS for 2 wk. During the sActRIIB-Fc-induced rapid 2-wk muscle growth period, oxidative capacity and autophagy were reduced, which may possibly explain the decreased running activity. These results show that increased muscle size and decreased markers of oxidative capacity and autophagy during the first weeks of myostatin/activin blocking are associated with decreased voluntary activity levels. Voluntary exercise in dystrophic mice enhances the markers of oxidative capacity and autophagy to or above the levels of healthy mice.
authors.affiliation: Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Finland. juha.hulmi@jyu.fi
authors.forename: Juha J
authors.initials: JJ
authors.lastname: Hulmi
authors.forename: Bernardo M
authors.initials: BM
authors.lastname: Oliveira
authors.forename: Mika
authors.initials: M
authors.lastname: Silvennoinen
authors.forename: Willem M H
authors.initials: WM
authors.lastname: Hoogaars
authors.forename: Arja
authors.initials: A
authors.lastname: Pasternack
authors.forename: Heikki
authors.initials: H
authors.lastname: Kainulainen
authors.forename: Olli
authors.initials: O
authors.lastname: Ritvos
mesh_terms: D030301:Activin Receptors, Type II / Q000096:biosynthesis / Q000494:pharmacology*; D028341:Activins / Q000037:antagonists & inhibitors* / Q000502:physiology; D050154:Adiposity / Q000235:genetics / Q000502:physiology; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D004247:DNA / Q000096:biosynthesis / Q000302:isolation & purification; D004435:Eating / Q000502:physiology; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009043:Motor Activity / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D055435:Myostatin / Q000037:antagonists & inhibitors* / Q000502:physiology; D010084:Oxidation-Reduction; D010805:Physical Conditioning, Animal / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D055435:Myostatin; D014409:Tumor Necrosis Factor-alpha; D028341:Activins; D004247:DNA; D002950:Citrate (si)-Synthase; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B; D003402:Creatine Kinase
keywords: activin receptor IIB; exercise; hypertrophy; myostatin; skeletal muscle