Effects of Exercise on Mitochondrial and Cardiometabolic Adaptations in Skeletal Muscle and Heart of Ovariectomized Rats

ABSTRACT Background Oestrogen deficiency after menopause is associated with metabolic dysfunction and increased cardiovascular risk, which may contribute to declines in skeletal muscle health and the development of postmenopausal sarcopenia. Mitochondria are central to energy metabolism and cellular adaptation and have indicated that oestrogen modulates mitochondrial biogenesis, oxidative phosphorylation and redox balance. Exercise training is considered a promising non‐pharmacological intervention to counteract these adverse effects by improving mitochondrial and metabolic health. However, studies directly evaluating mitochondrial adaptations to exercise under oestrogen‐deficient conditions remain limited, and existing findings are inconsistent across experimental models. Methods Female Sprague–Dawley rats were randomly assigned to four groups: sham‐operated (S, n = 6), ovariectomy (O, n = 6), sham plus exercise (SE, n = 8) and ovariectomy plus exercise (OE, n = 8). Exercise training consisted of treadmill running (28 m/min, 60 min/day, 5 days/week) for 12 weeks. Body weight, uterine mass, metabolic parameters, aerobic capacity, mitochondrial‐related proteins and cardiac fibrosis were measured and analysed. Results Ovariectomy resulted in significant body weight gain ( p < 0.001) and uterine atrophy ( p < 0.001) compared with sham controls. After exercise training, peak V̇O 2 was significantly higher in exercise groups ( p < 0.001), indicating improved aerobic capacity under oestrogen‐deficient conditions. Serum glucose levels were markedly increased in OVX rats ( p < 0.001) and were partially normalized by exercise training ( p < 0.05). Serum growth differentiation factor 15 (GDF‐15) levels were elevated in the O group ( p < 0.01). Several mitochondrial electron transport chain (ETC) complexes were significantly upregulated in the SE group compared with the S and O groups ( p < 0.01), and Complex III expression was significantly higher in the OE group than in the O group ( p < 0.01). Complex IV showed only partial recovery in the OE group ( p < 0.05), and Complex V remained unchanged. Expression of pyruvate metabolism–related proteins was significantly lower in the O group ( p < 0.01), although both exercise groups showed higher expression levels than the O group ( p < 0.05). The expression of the mitochondrial biogenesis marker peroxisome proliferator–activated receptor‐γ coactivator‐1α (PGC‐1α) was significantly reduced in the O group ( p < 0.01) but was partially restored by exercise training. Histological analysis demonstrated a marked increase in myocardial fibrosis in the O group ( p < 0.001), which was significantly attenuated by exercise in the OE group ( p < 0.001). Conclusion Exercise training improved aerobic capacity, induced selective mitochondrial protein adaptations and attenuated myocardial fibrosis under oestrogen‐deficient conditions, supporting its potential as a non‐pharmacological intervention in postmenopausal settings.