High-intensity interval training improves fatty infiltration in the rotator cuff through the β3 adrenergic receptor in mice

by Selleckchem | Nov 25 2023

Aims: Rotator cuff muscle atrophy and fatty infiltration affect the clinical outcomes of rotator cuff tear patients. However, there is no effective treatment for fatty infiltration at this time. High-intensity interval training (HIIT) helps to activate beige adipose tissue. The goal of this study was to test the role of HIIT in improving muscle quality in a rotator cuff tear model via the β3 adrenergic receptor (β3AR).

Methods: Three-month-old C57BL/6 J mice underwent a unilateral rotator cuff injury procedure. Mice were forced to run on a treadmill with the HIIT programme during the first to sixth weeks or seventh to 12th weeks after tendon tear surgery. To study the role of β3AR, SR59230A, a selective β3AR antagonist, was administered to mice ten minutes before each exercise through intraperitoneal injection. Supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat were harvested at the end of the 12th week after tendon tear and analyzed biomechanically, histologically, and biochemically.

Results: Histological analysis of supraspinatus muscle showed that HIIT improved muscle atrophy, fatty infiltration, and contractile force compared to the no exercise group. In the HIIT groups, supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat showed increased expression of tyrosine hydroxylase and uncoupling protein 1, and upregulated the β3AR thermogenesis pathway. However, the effect of HIIT was not present in mice injected with SR59230A, suggesting that HIIT affected muscles via β3AR.

Conclusion: HIIT improved supraspinatus muscle quality and function after rotator cuff tears by activating systemic sympathetic nerve fibre near adipocytes and β3AR.

Comments:

The provided study investigates the potential benefits of High-Intensity Interval Training (HIIT) in improving muscle quality in a rotator cuff tear model. Here's a summary of the study's objectives, methods, and findings:

**Objective:**
The study aimed to assess the impact of High-Intensity Interval Training (HIIT) on muscle quality in a mouse model of rotator cuff tear, particularly focusing on muscle atrophy and fatty infiltration. Additionally, the study aimed to explore the involvement of the β3 adrenergic receptor (β3AR) in the effects of HIIT.

**Methods:**
- **Participants:** Three-month-old C57BL/6 J mice.
- **Procedure:** Unilateral rotator cuff injury was induced in the mice.
- **Intervention:** Mice were subjected to HIIT on a treadmill during specific time frames after the tendon tear surgery.
- **β3AR Blockade:** To investigate the role of β3AR, a selective β3AR antagonist (SR59230A) was administered to mice before each exercise session via intraperitoneal injection.
- **Analysis:** Muscle tissues (supraspinatus muscle) as well as brown fat (interscapular) and white fat (inguinal subcutaneous) were harvested and analyzed biomechanically, histologically, and biochemically.

**Results:**
- **Muscle Improvement:** HIIT led to improvements in muscle atrophy, fatty infiltration, and contractile force in the supraspinatus muscle compared to the no-exercise group.
- **Expression Changes:** HIIT increased the expression of tyrosine hydroxylase and uncoupling protein 1, indicating activation of the β3AR thermogenesis pathway, in supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat.
- **Role of β3AR:** The positive effects of HIIT were negated in mice injected with the β3AR antagonist SR59230A, suggesting that HIIT influenced muscles via the β3AR pathway.

**Conclusion:**
High-Intensity Interval Training (HIIT) was found to enhance the quality and function of the supraspinatus muscle after rotator cuff tears. This improvement occurred through the activation of systemic sympathetic nerve fibers near adipocytes and the β3 adrenergic receptor (β3AR) pathway. The study implies that HIIT might be a potential therapeutic approach for improving muscle quality in patients with rotator cuff tears.