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- Title
Brown/Beige Fat Activation after Skeletal Muscle Ischemia-Reperfusion Injury.
- Authors
Liu, M.; Wang, Z.; Lee, C. S.; Nguyen, C.; Lee, L.; Kim, H. T.; Feeley, B. T.; Liu, X.
- Abstract
Objective. Skeletal muscle Ischemia-Reperfusion Injury (IRI) is a commonly seen orthopedic injury. However, the role of The Brown/Beige Adipose Tissue (BAT) in muscle regeneration after IRI remains unknown. In this study, we assessed the role of BAT in muscle regeneration using UCP-1 reporter and Knockout (KO) mice. We hypothesize that UCP-1 expression increases in BAT after muscle injury and UCP-1 KO mice have reduced muscle regeneration after IRI. Methods. Unilateral hindlimb IRI was performed on mice by applying a rubber band on the thigh for three hours. Amibegron and antagonist, which activates/deactivates BAT, were also given to mice after IRI. DigiGait analysis was performed at 2 or 4 weeks after IR injury. White (epidydimal) fat, brown (interscapular) fat, beige (inguinal) fat and gastrocnemius muscles on both injury and contralateral uninjured sides were harvested. Muscle regeneration index, RT-PCR were performed on brown, beige and white fat to evaluate promyogenic growth factor gene expression. Results. After hindlimb IRI, UCP-1 expression increased in brown, beige and white fat, which was accompanied by increase of gene expression promyogenic growth factors of IGF1 and follistatin. IRI also induced UCP-1 expression in both injured and contralateral uninjured muscle. DigiGait analysis demonstrated significantly decreased (p < 0.05) hindlimb function at 2 weeks post-injury in UCP-1 KO mice compared to wildtype mice. Muscle histology showed significantly reduced muscle regeneration in UCP-1 KO mice compared to WT mice. Amibegron activates BAT and improves muscle regeneration, while SR-59230A deactivates BAT and reduced muscle regeneration after IRI. Conclusions. BAT plays an important role in muscle regeneration of IRI. Pro-myogenic batokines from BAT may be the mediator for muscle regeneration after IRI. β3 adrenergic receptor agonists may be novel treatment for muscle IRI in the future.
- Publication
Muscles, Ligaments & Tendons Journal (MLTJ), 2020, Vol 10, Issue 4, p579
- ISSN
2240-4554
- Publication type
Academic Journal
- DOI
10.32098/mltj.04.2020.05