Aerobic Training Alleviates Muscle Atrophy by Promoting the Proliferation of Skeletal Muscle Satellite Cells in Myotonic Dystrophy Type 1 by Inhibiting Glycolysis

backgroundSkeletal muscle atrophy in myotonic dystrophy type 1 (DM1) is caused by abnormal skeletal muscle satellite cell (SSC) proliferation due to increased glycolysis, which impairs muscle regeneration. In DM1, RNA foci sequester muscleblind-like protein 1 (MBNL1) in the nucleus, inhibiting its role in regulating SSC proliferation. Aerobic training reduces glycolysis and increases SSC proliferation and muscle fiber volume. This study aimed to investigate whether aerobic training prevents muscle atrophy in DM1 through the regulation of glycolysis

methodsIn this study, we used the HSA

resultsAerobic training increased hindlimb grip strength and the average myofiber CSA in DM1 mice. Additionally, aerobic training reduced RNA foci, upregulated MBNL1, and promoted SSC proliferation. Gene set enrichment analysis (GSEA) indicated that glycolytic processes were enriched following the knockdown of MBNL1. Furthermore, ECAR showed glycolysis was enhanced after the knockdown of MBNL1. Aerobic training reduced elevated glycolysis in DM1 mice and primary SSCs. Treatment with shikonin promoted DM1 SSC proliferation. However, MBNL1 knockdown was shown to abolish the reduced glycolysis and increased proliferation capability of SSCs due to aerobic training.

conclusionTaken together, aerobic training suppresses glycolysis in SSCs via the upregulation of MBNL1, thereby enhancing SSC proliferation and alleviating muscle atrophy.