The CB1 antagonist Rimonabant improves muscle regeneration and remodels the inflammatory and endocannabinoid profile upon injury in male mice.

Autor: Dalle S; Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Tervuursevest 101, 3001 Leuven, Belgium; MOVANT Research Group, Department of Rehabilitation Sciences and Physiotherapy, University of Antwerp, Antwerp, Belgium. Electronic address: Sebastiaan.dalle@kuleuven.be., Schouten M; Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Tervuursevest 101, 3001 Leuven, Belgium. Electronic address: Moniek.schouten@kuleuven.be., Vanderbeke K; Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Tervuursevest 101, 3001 Leuven, Belgium. Electronic address: Kaat.vanderbeke@kuleuven.be., Van Parys E; Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Tervuursevest 101, 3001 Leuven, Belgium., Ramaekers M; Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Tervuursevest 101, 3001 Leuven, Belgium. Electronic address: Monique.ramaekers@kuleuven.be., Thomis M; Physical Activity, Sports & Health Research Group, Department of Movement Sciences, KU Leuven, Tervuursevest 101, 3001 Leuven, Belgium., Costamagna D; Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Tervuursevest 101, 3001 Leuven, Belgium. Electronic address: Domiziana.costamagna@kuleuven.be., Koppo K; Exercise Physiology Research Group, Department of Movement Sciences, KU Leuven, Tervuursevest 101, 3001 Leuven, Belgium. Electronic address: Katrien.koppo@kuleuven.be.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2024 Dec 05, pp. 123296. Date of Electronic Publication: 2024 Dec 05.
DOI: 10.1016/j.lfs.2024.123296
Abstrakt: 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 the CB1 antagonist Rimonabant (10 mg/kg/d) on functional (5 days post-cardiotoxin injury; 5DPI) and molecular muscle responses (3DPI and 7DPI) in mice. Rimonabant prevented cardiotoxin-induced muscle strength loss 5DPI, increased myofiber growth (7DPI) and improved the muscle molecular profile 3DPI and 7DPI. In general, inflammation (e.g. p-p65NF-κB, CD80) and apoptosis (e.g. cleaved caspase-3, cleaved PARP) were downregulated by Rimonabant, whereas it upregulated the expression of Pax7 but other myogenic factors remained unaffected by rimonabant. In addition, Rimonabant restored the injury-induced (inflammatory) lipid profile to a large extent, including oxygenated fatty acids, unsaturated fatty acids and endocannabinoids such as 2-arachidonoyl glycerol and palmitoylethanolamide. Altogether, these data show that the endocannabinoid system might be a novel therapeutic target to improve muscle regeneration, which is relevant for age- and disease-related muscle degeneration.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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