(PTFS01-02-24) Investigating Metabolic Profiles in Mouse Skeletal Muscle Regeneration

Objectives: Muscle injuries are common and underline the essential for continuous muscle regeneration to maintain strength and mobility. Metabolic switches play a crucial role in cellular development and regeneration. In response to changes in physiological state, cells undergo metabolic switching that is necessary for growth and repair. However, the specifics of metabolic profiles during skeletal muscle regeneration in mice, including how sex differences affect these profiles and regeneration capacities, remain unclear. Our study aims to identify a comprehensive metabolite profile involved in skeletal muscle regeneration by comparing the regenerative capabilities of injured skeletal muscle.

Methods: We utilized 8-weeks-old male and female C57BL/6 mice, divided into control and muscle-injured groups. Muscle injury was induced using cardiotoxin (CTX), while saline injections used as controls. Tibialis anterior (TA) muscles were collected at 7- and 21-days post-injury (dpi) for targeting metabolomics analysis and histological examination, respectively.

Results: Our findings indicate metabolic shifts in glycolytic and TCA cycle intermediates at 7 dpi. Amino acids including alanine and glutamine were upregulated in injured TA muscles compared to controls. Remarkably, metabolite levels differed between male and female mice in the TA muscle. Injured muscles in female mice showed decreases in glycolytic intermediates such as D-glucose 6-phosphate, D-fructose 6-phosphate, and 3-phosphoglyceric acid, while male mice showed an increase or no change in glycolytic intermediates. Furthermore, phosphoenol pyruvate and lactic acid levels significantly decreased in CTX-injured female mice, with no significant difference observed in male mice. Histology analysis using Trichrome staining at 21 dpi showed nearly complete regeneration in the male injured groups, whereas the female injury group did not complete regeneration.

Conclusions: Our study concludes that glycolytic intermediates play a crucial role in the skeletal muscle regeneration following injury. These findings suggest that the differences in skeletal muscle injury between sexes significantly affect metabolic profiles and the regeneration process.

Funding Sources: OSU Start-up, OSU One Health, OCASCR Research grants to J.B.