Effect of High-Intensity Interval Training on Fatty Infiltration After Delayed Rotator Cuff Repair in a Mouse Model

Abstract

Background: Fatty infiltration (FI) of the rotator cuff muscles is correlated with shoulder function and retear rates after rotator cuff repair. High-intensity interval training (HIIT) induces beige adipose tissue to express more uncoupling protein 1 (UCP1) to consume lipids. The beta-3 adrenergic receptor (β3AR) is located on adipocyte membrane and induces thermogenesis. Purpose: To test the role of HIIT in improving muscle quality and contractility in a delayed rotator cuff repair mouse model via β3AR. Study Design: Controlled laboratory study. Methods: Three-month-old C57BL/6J mice underwent a unilateral supraspinatus (SS) tendon transection with a 6-week delayed tendon repair. Mice ran on a treadmill with the HIIT program for 6 weeks after tendon transection or after delayed repair. To study the role of β3AR, SR59230A, a selective β3AR antagonist, was administered to mice 10 minutes before each exercise through intraperitoneal injection. The SS, interscapular brown adipose tissue (iBAT), and subcutaneous inguinal white adipose tissue (ingWAT) were harvested at the end of the 12th week after tendon transection and were analyzed by histology and Western blotting. Tests were performed to assess muscle contractility of the SS. Results: Histologic analysis of SS showed that HIIT prevented and reversed muscle atrophy and FI. The contractile tests showed higher contractility of the SS in the HIIT groups than in the no-exercise group. In the HIIT groups, SS, iBAT, and ingWAT all showed increased expression of tyrosine hydroxylase, UCP1, and upregulated β3AR thermogenesis pathway. However, SR59230A inhibited HIIT, suggesting that the effect of HIIT depends on β3AR. Conclusion: HIIT improved SS quality and function after delayed rotator cuff repair through a β3AR-dependent mechanism. Clinical Relevance: HIIT may serve as a new rehabilitation method for patients with rotator cuff muscle atrophy and FI after rotator cuff repair to improve postoperative clinical outcomes.