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

Stefania Banfi, Giuseppe D’Antona, Chiara Ruocco, Mirella Meregalli, Marzia Belicchi, Pamela Bella, Silvia Erratico, Elisa Donato, Fabio Rossi, Francesco Bifari, Caterina Lonati, Stefano Campaner, Enzo Nisoli, Yvan Torrente

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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.

Original languageEnglish
Article number14659
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

ASJC Scopus subject areas

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    Banfi, S., D’Antona, G., Ruocco, C., Meregalli, M., Belicchi, M., Bella, P., Erratico, S., Donato, E., Rossi, F., Bifari, F., Lonati, C., Campaner, S., Nisoli, E., & Torrente, Y. (2018). Supplementation with a selective amino acid formula ameliorates muscular dystrophy in mdx mice. Scientific Reports, 8(1), [14659]. https://doi.org/10.1038/s41598-018-32613-w