Supplementation with a selective amino acid formula ameliorates muscular dystrophy in mdx mice

Sci Rep. 2018 Oct 2;8(1):14659. doi: 10.1038/s41598-018-32613-w.

Abstract

Duchenne muscular dystrophy (DMD) is one of the most common and severe forms of muscular dystrophy. Oxidative myofibre content, muscle vasculature architecture and exercise tolerance are impaired in DMD. Several studies have demonstrated that nutrient supplements ameliorate dystrophic features, thereby enhancing muscle performance. Here, we report that dietary supplementation with a specific branched-chain amino acid-enriched mixture (BCAAem) increased the abundance of oxidative muscle fibres associated with increased muscle endurance in dystrophic mdx mice. Amelioration of the fatigue index in BCAAem-treated mdx mice was caused by a cascade of events in the muscle tissue, which were promoted by endothelial nitric oxide synthase (eNOS) activation and vascular endothelial growth factor (VEGF) expression. VEGF induction led to recruitment of bone marrow (BM)-derived endothelial progenitors (EPs), which increased the capillary density of dystrophic skeletal muscle. Functionally, BCAAem mitigated the dystrophic phenotype of mdx mice without inducing dystrophin protein expression or replacing the dystrophin-associated glycoprotein (DAG) complex in the membrane, which is typically lost in DMD. BCAAem supplementation could be an effective adjuvant strategy in DMD treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / administration & dosage*
  • Animals
  • Dietary Supplements*
  • Disease Models, Animal
  • Endothelial Progenitor Cells / drug effects
  • Endothelial Progenitor Cells / metabolism
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Mice, Knockout
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle Strength / drug effects
  • Muscular Dystrophy, Duchenne / diet therapy*
  • Muscular Dystrophy, Duchenne / genetics
  • Muscular Dystrophy, Duchenne / pathology
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress / drug effects
  • Physical Endurance / drug effects
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Amino Acids
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse