(P04-018-25) Glycolytic Metabolic Differences Influence Skeletal Muscle Regeneration Following Injury

Objectives: Skeletal muscle injuries occur repeatedly throughout life, emphasizing the importance of continuous muscle regeneration for maintaining strength and mobility. However, research on the metabolic mechanisms driving muscle recovery remains limited. Recent findings suggest that sex-based differences may impact these mechanisms and recovery outcomes. This study aims to investigate how sex-based differences influence skeletal muscle regeneration by analyzing glycolytic intermediates, amino acids, and molecular and histological markers.

Methods: Eight-week-old C57BL/6 mice were divided into male, female, control, and injury groups. Muscle injury was induced via cardiotoxin injection, and tibialis anterior (TA) muscles were collected at 7 and 21 days post-injury. Metabolomic profiling analyzed glycolytic intermediates and amino acid metabolites. Western blotting quantified glycolysis-related proteins, and qPCR assessed muscle regeneration-associated genes. Histological analysis, including hematoxylin and eosin (H&E) and Masson’s trichrome staining, evaluated tissue morphology and fibrosis.

Results: Our findings revealed that sex-based metabolic differences significantly influenced muscle regeneration after injury. Metabolomic analysis identified distinct variations in glycolytic intermediates and amino acids between sexes. Gene expression analysis showed higher Pax7 and MyoG levels in both sexes, with males exhibiting a stronger MyoG response, indicating enhanced muscle cell differentiation. Females displayed delayed recovery at 7 days post-injury, with reduced TA muscle weight and increased inflammation and fibrosis. Western blot analysis suggested sex-specific glycolytic protein differences, highlighting a metabolic role in recovery.

Conclusions: Our study highlights significant sex-based differences in glucose metabolism that influence skeletal muscle regeneration following injury. Males showed stronger early regenerative responses, whereas females showed delayed recovery possibly due to differences in glucose metabolism and regenerative gene expression markers.

Funding Sources: This study was supported by the Oklahoma Center for Adult Stem Cell Research, the One Health Project by the OSU Vice President for Research, and the American Heart Association.