Dystropathology increases energy expenditure and protein turnover in the mdx mouse model of duchenne muscular dystrophy

PLoS One. 2014 Feb 19;9(2):e89277. doi: 10.1371/journal.pone.0089277. eCollection 2014.


The skeletal muscles in Duchenne muscular dystrophy and the mdx mouse model lack functional dystrophin and undergo repeated bouts of necrosis, regeneration, and growth. These processes have a high metabolic cost. However, the consequences for whole body energy and protein metabolism, and on the dietary requirements for these macronutrients at different stages of the disease, are not well-understood. This study used juvenile (4- to 5- wk-old) and adult (12- to 14-wk-old) male dystrophic C57BL/10ScSn-mdx/J and age-matched C57BL/10ScSn/J control male mice to measure total and resting energy expenditure, food intake, spontaneous activity, body composition, whole body protein turnover, and muscle protein synthesis rates. In juvenile mdx mice that have extensive muscle damage, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were higher than in age-matched controls. Adaptations in food intake and decreased activity were insufficient to meet the increased energy and protein needs of juvenile mdx mice and resulted in stunted growth. In (non-growing) adult mdx mice with less severe dystropathology, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were also higher than in age-matched controls. Food intake was sufficient to meet their protein and energy needs, but insufficient to result in fat deposition. These data show that dystropathology impacts the protein and energy needs of mdx mice and that tailored dietary interventions are necessary to redress this imbalance. If not met, the resultant imbalance blunts growth, and may limit the benefits of therapies designed to protect and repair dystrophic muscles.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age Factors
  • Analysis of Variance
  • Animals
  • Body Composition / physiology
  • Eating / physiology
  • Energy Metabolism / physiology*
  • Female
  • Male
  • Mice
  • Mice, Inbred mdx
  • Models, Biological
  • Muscle, Skeletal / physiology*
  • Muscular Dystrophy, Duchenne / physiopathology*
  • Protein Biosynthesis / physiology*

Grant support

H. Radley-Crabb was supported by an Australian Postgraduate Award and a Grant for Research Student Training provided by UWA. Support for isotope analyses was provided by USDA/ARS funds. Body composition, energy balance, and food intake measurements were performed in the Mouse Metabolic Research Unit at the USDA/ARS Children’s Nutrition Research Center, which is supported by funds from the USDA/ARS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.