Lipid mediator abundance in injured vs. uninjured skeletal muscle of male C57BL/6 mice

Skeletal muscle regeneration upon injury requires timely activation of inflammatory, myogenic, fibrotic, apoptotic and anabolic systems. Optimization of these features might improve the recovery process. Whereas recent data indicate that the endocannabinoid system, and more particularly cannabinoid receptor 1 (CB1) antagonism, is involved in the regulation of inflammatory, myogenic, fibrotic, apoptotic and anabolic pathways, it was never studied whether CB1 antagonism can improve muscle regeneration. The present study investigated the effect of injury and of treatment with the CB1 antagonist Rimonabant (10 mg/kg/d) on the skeletal muscle lipidomic mediator abundance at 3 days and 7 days post-injury. Injury was induced via cardiotoxin injection in the m. Gastrocnemius (50 µL; 10 µM dissolved in saline), whereas uninjured control mice received an intramuscular saline injection (50µL). At both time point following intramuscular injection (i.e. 3 & 7 days), 3 control muscles, 6 injured + untreated muscles and 6 injured + Rimonabant treated muscles were sampled for lipidomic analyses. Lipid extraction and the LC-MS/MS–based lipidomics was performed by the KU Leuven Lipometrix core facility. More detail is provided in Dalle, S., Schouten, M., Vanderbeke, K., van Parys, E., Ramaekers, M., Thomis, M., Costamagna, D., & Koppo, K. (2025). The CB1 antagonist Rimonabant improves muscle regeneration and remodels the inflammatory and endocannabinoid profile upon injury in male mice. Life Sciences, 361, 123296. https://doi.org/10.1016/j.lfs.2024.123296