Low-intensity exercise modulates skeletal muscle in a HFpEF animal model
L Brochado, D Moreira Goncalves, I Pires Marques, I Miranda, A Leite MoreiraAbstract
Introduction
Heart failure with preserved ejection fraction (HFpEF) affects approximately 50% of patients with heart failure (HF), shows increasing prevalence with population aging, and lacks effective therapeutic options. Its diagnosis is challenging due to the nonspecific nature of symptoms and the presence of multiple comorbidities. One of the cardinal features of HFpEF is reduced exercise tolerance, which correlates with poorer quality of life and adverse prognosis. Paradoxically, regular physical exercise has been shown to improve cardiorespiratory fitness and quality of life in patients with HFpEF. The underlying mechanisms are not yet fully understood; however, a central role has been attributed to exercise-induced changes in skeletal muscle.
Objective
To study the impact of a low-intensity physical exercise program on morphological and biochemical alterations of skeletal muscle in an animal model of HFpEF.
Materials and Methods
Ten obese ZSF1 rats (Ob) (age = 15 weeks) were randomly divided into a sedentary obese group (ObSED, n = 5; remained sedentary in their cages) and an exercise obese group (ObEX, n = 5; subjected to a training protocol for 5 weeks, 5 days/week, 60 min/day, at 20 m/min). Additionally, four lean ZSF1 rats (Lean, n = 4) were included as pathological controls. At the end of the protocol (20th week), all animals underwent a maximal oxygen consumption (VO₂max) test, were euthanized, and soleus muscle samples were collected for histological and biochemical analysis.
Results
We found that animals in the ObSED group exhibited a significant reduction in the cross-sectional area of the soleus muscle (P < 0.05 vs. Lean), and that physical exercise was able to reverse this alteration in the ObEX group (P < 0.05 vs. ObSED). Regarding fibrosis, an increase in its levels was observed in the ObSED group (P < 0.05 vs. Lean), and once again exercise was able to reverse/prevent this increase (P < 0.05 vs. ObSED). No statistically significant differences were observed among the groups in the expression of proteins involved in hypertrophy (AKT, ERK1, and ERK2) and cell death (Bcl-xL). The ObEX group demonstrated a tendency toward increased phosphorylation of MyBP-C and reduced phosphorylation of TnI.
Conclusion
The results suggest that regular physical exercise reverses muscle atrophy associated with HFpEF. These structural changes in skeletal muscle may account for the increase in arteriovenous oxygen difference (A–VO₂) in animals with HFpEF, potentially complementing the explanation for the increase in peak VO₂ observed in patients with HFpEF.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.