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Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice

Hulmi, Juha J; Moreira Soares Oliveira, Bernardo LU ; Silvennoinen, Mika; Hoogaars, Willem M H; Pasternack, Arja; Kainulainen, Heikki and Ritvos, Olli (2013) In American Journal of Physiology - Endocrinology and Metabolism 305(2). p.82-171
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... (More)

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.

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author
publishing date
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Contribution to journal
publication status
published
keywords
Activin Receptors, Type II, Activins, Adiposity, Animals, Autophagy, Blotting, Western, Body Weight, Citrate (si)-Synthase, Creatine Kinase, DNA, Eating, Hematocrit, Hemoglobins, Mice, Mice, Inbred C57BL, Mice, Inbred mdx, Motor Activity, Muscle, Skeletal, Myostatin, Oxidation-Reduction, Physical Conditioning, Animal, Tumor Necrosis Factor-alpha, Journal Article, Research Support, Non-U.S. Gov't
in
American Journal of Physiology - Endocrinology and Metabolism
volume
305
issue
2
pages
82 - 171
publisher
American Physiological Society
external identifiers
  • scopus:84880166921
ISSN
1522-1555
DOI
10.1152/ajpendo.00065.2013
language
English
LU publication?
no
id
1d42bc6a-2a96-40ee-bc94-a291cdb0eb11
date added to LUP
2017-03-08 14:39:08
date last changed
2019-07-16 03:18:16
@article{1d42bc6a-2a96-40ee-bc94-a291cdb0eb11,
  abstract     = {<p>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.</p>},
  author       = {Hulmi, Juha J and Moreira Soares Oliveira, Bernardo and Silvennoinen, Mika and Hoogaars, Willem M H and Pasternack, Arja and Kainulainen, Heikki and Ritvos, Olli},
  issn         = {1522-1555},
  keyword      = {Activin Receptors, Type II,Activins,Adiposity,Animals,Autophagy,Blotting, Western,Body Weight,Citrate (si)-Synthase,Creatine Kinase,DNA,Eating,Hematocrit,Hemoglobins,Mice,Mice, Inbred C57BL,Mice, Inbred mdx,Motor Activity,Muscle, Skeletal,Myostatin,Oxidation-Reduction,Physical Conditioning, Animal,Tumor Necrosis Factor-alpha,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {07},
  number       = {2},
  pages        = {82--171},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology - Endocrinology and Metabolism},
  title        = {Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice},
  url          = {http://dx.doi.org/10.1152/ajpendo.00065.2013},
  volume       = {305},
  year         = {2013},
}