The flavanol (-)-epicatechin induced different histological features and myogenic protein levels in triceps, gastrocnemius and plantaris of δ-sarcoglycan-deficient mice.

Limb-girdle muscular dystrophies (LGMD) exhibit a wide range of disease severity, affecting various parts of the skeletal muscle to varying degrees. This may be associated with differences in the degeneration and regeneration processes in different muscles. We previously reported that muscles with different metabolic characteristics showed distinct levels of proteins involved in the muscle regeneration process in δ-sarcoglycan-deficient mice, a model for LGMDR6. These phenomena may be relevant to test potential therapeutic compounds in myopathies. In this study, we analyzed the effect of (-)-epicatechin (Epi), a flavanol enriched in cacao that has shown beneficial effects in skeletal muscle, in different muscles of the δ-sarcoglycan-deficient mice. Histochemical analysis showed that dystrophic triceps and gastrocnemius had a higher level of fibrosis than plantaris, and Epi reduced this. In addition, Epi increased the cross-sectional area of dystrophic triceps fibers, which was associated with a higher fusion index. In contrast, Epi reduced the index fusion in dystrophic plantaris. Western blot analysis demonstrates that Epi increases protein levels of Pax7, β-catenin, and myogenin in the dystrophic triceps and increases protein levels of β-catenin and myogenin in the gastrocnemius. In contrast, in the plantaris, none of the protein levels was modified. All these results suggest that muscles with different metabolic characteristics and physiological demands could respond differentially to pharmacological therapies in dystrophic muscles.