Myostatin/activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice

•Decreased aerobic metabolism in mdx mice, not due to reduced physical activity.•Aerobic metabolism was further decreased by myostatin/activin blocking.•Exercise counteracted these effects of myostatin/activin blocking.•Exercise activated pathways of aerobic metabolism in mdx mice toward wild types.•Combination of exercise and myostatin/activin blocking affected pSTAT5 and MUP.

Duchenne muscular dystrophy is characterized by muscle wasting and decreased aerobic metabolism. Exercise and blocking of myostatin/activin signaling may independently or combined counteract muscle wasting and dystrophies. The effects of myostatin/activin blocking using soluble activin receptor-Fc (sActRIIB-Fc) administration and wheel running were tested alone or in combination for 7 weeks in dystrophic mdx mice. Expression microarray analysis revealed decreased aerobic metabolism in the gastrocnemius muscle of mdx mice compared to healthy mice. This was not due to reduced home-cage physical activity, and was further downregulated upon sActRIIB-Fc treatment in enlarged muscles. However, exercise activated pathways of aerobic metabolism and counteracted the negative effects of sActRIIB-Fc. Exercise and sActRIIB-Fc synergistically increased expression of major urinary protein, but exercise blocked sActRIIB-Fc induced phosphorylation of STAT5 in gastrocnemius muscle. In conclusion, exercise alone or in combination with myostatin/activin blocking corrects aerobic gene expression profiles of dystrophic muscle toward healthy wild type mice profiles.