Long‐term Dietary Quercetin Enrichment Improves Muscle Function in Dystrophic Skeletal Muscle

Abstract

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease characterized by progressive muscle injury culminating in loss of ambulation and death. It is now clear that increased muscle PGC‐1α pathway activity improves many aspects of disease pathology. Translating this work to human patients necessitates identification of a safe PGC‐1α activator. The purpose of this investigation was to determine the extent to which dietary enrichment of quercetin, a known PGC‐1α activator, improved skeletal muscle function in mdx mice, a model of DMD. mdx mice were maintained on a control or 0.2% quercetin‐enriched diet from two to 14 months of age before sacrifice and tissue collection. Healthy, C57 mice were maintained on a control diet. At 14 months of age body weight was decreased by 12% (p<0.05) in mdx and by 20% in mdxQ (p<0.05 v C57 and mdx) compared to C57. Soleus muscle mass was increased by 35 and 30% (p<0.05) in mdx and mdxQ, respectively, compared to C57. Tetanic force was similar between all groups. Importantly, dietary quercetin enrichment decreased the 42% reduction in specific tension in the mdx soleus compared to C57 by half (p<0.05). In soleus muscle from mdx mice the force produced during the final contraction of a 10 minute fatigue protocol was 8% of the initial force while that of C57 was 16% (p<0.05). Force produced by mdxQ was 12% of initial force though was similar to both groups. In total, these data clearly indicate that long‐term dietary quercetin enrichment provides a benefit to soleus muscle function and should be considered as part of a therapeutic regimen for DMD patients. Supported by the Duchenne Alliance.