SUMMARY
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.
Brown/Beige Fat Activation after Skeletal Muscle Ischemia-Reperfusion Injury
M. Liu, Z. Wang, C. S. Lee, C. Nguyen, L. Lee, H. T. Kim, B. T. Feeley, X. Liu
Original Article, 579-588
Keywords: Brown fat; beige fat; ischemia-reperfusion injury; muscle; regeneration; uncoupling protein-1,
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