Effects of high-intensity interval training combined with estrogen on satellite cells, myonuclear domain and ribosome function in ovariectomized rats

Abstract

BACKGROUND: Estrogen deficiency can lead to a decrease in skeletal muscle mass and muscle strength in postmenopausal women, thereby affecting their quality of life. Muscle mass is maintained by satellite cells, which are regulated by estrogen. Regular exercise, especially high impact exercise (such as resistance training and high-intensity interval training), can induce muscle hypertrophy, but the role and mechanism of estrogen are still unclear. OBJECTIVE: To explore the effects of high-intensity interval training combined with estrogen therapy on skeletal muscle hypertrophy in ovariectomized rats and reveal its possible mechanism. METHODS: Sixty 8-week-old female Sprague-Dawley rats were divided into five groups using a random number table method: sham operation, model sedentary group, model exercise group, model hormone group, or model combined group. Bilateral ovariectomy was used to establish an estrogen deficiency model. Twelve weeks after operation, the model exercise and model combined group performed high-intensity interval training for 8 weeks (3 times/week), and hormone treatment groups received abdominal subcutaneous injection of 17β-estradiol (once a day for 8 weeks). Seventy-two hours after the last training, the grip force of the forelimb was measured by an electronic grip force meter. The gastrocnemius muscle was separated, and muscle mass index was calculated as muscle mass/body mass ratio. Hematoxylin-eosin staining was used to obtain cell cross-sectional area. Immunofluorescence staining was used to classify muscle fiber types and obtain myonuclear number, myonuclear domain size, and activated satellite cell number. BCA method was used to determine total protein concentration. Trizol method was used to extract total RNA. Western blot was used to detect ribosomal protein S6 expression. Real-time quantitative PCR was used to detect ribosomal RNA expression. RESULTS AND CONCLUSION: Compared with the sham operation group, the model sedentary group showed increased body mass and myosin heavy chain type I fiber proportion (P < 0.05), while uterine mass index, gastrocnemius mass index, grip strength, cell cross-sectional area, myosin heavy chain type IIa proportion, satellite cell and myonuclear number, myonuclear domain size, total protein and RNA content, and ribosomal protein S6, 18S rRNA and 28S rRNA expression decreased (P < 0.05). Compared with the model sedentary group, the model exercise group showed decreased body mass and myosin heavy chain type IIb proportion (P < 0.05), while uterine mass index, gastrocnemius mass index, grip strength, cell cross-sectional area, myosin heavy chain type IIa proportion, satellite cell number, myonuclear domain size, total protein and RNA content, and ribosomal protein S6 and 28S rRNA expression increased (P < 0.05). Compared with the model exercise group and model hormone group, the model combined group showed higher gastrocnemius mass index, grip strength, cell cross-sectional area, satellite cell number, myonuclear domain size, total protein and RNA content, and ribosomal protein S6 and 28S rRNA expression (P < 0.05). These results indicate that estrogen can enhance the skeletal muscle hypertrophy response induced by high-intensity interval training in ovariectomized rats, and the mechanism may be related to satellite cell activation, increased myonuclear domain and ribosome biogenesis, and improved ribosome function.

1. Introduction

With aging, there is a gradual decline in muscle mass and strength, known as sarcopenia [1]. Compared with young women, postmenopausal women have lower lean body mass, physical activity levels, and muscle mass, ultimately leading to decreased physical function and quality of life. This suggests that estrogen deficiency after menopause may be a key cause of muscle loss in older women [2]. Exercise is an important mechanical stimulus for muscle health. For patients with sarcopenia, resistance training is generally recommended as the primary mode to improve muscle mass [3], while the effects of other exercise modalities remain to be confirmed. Traditional aerobic exercise has low intensity and generally improves muscle endurance, but has minimal effect on inducing muscle hypertrophy [4]. Since high-impact exercises such as explosive movements (e.g., jumping) and eccentric exercises (e.g., downhill running) also have muscle-building effects [4], developing high-impact exercise modalities may help enrich the exercise rehabilitation prescriptions for sarcopenia patients.

High-intensity interval training (HIIT) is a recently developed training method that alternates between high-intensity and low-intensity exercise in short bursts, and is also classified as high-impact exercise, with significant time efficiency as its main feature [5]. The beneficial effects of HIIT on cardiorespiratory fitness have been widely confirmed [6], but its effects on skeletal muscle and the underlying mechanisms remain unclear. It is known that the mechanisms by which HIIT induces muscle hypertrophy are complex, involving multiple cellular and molecular changes. In terms of energy metabolism, HIIT can significantly increase muscle glycogen utilization,