Aerobic exercise induces selective changes in skeletal muscle protein quality control markers in rats with heart failure

Abstract

The objective of this study was to determine whether aerobic exercise could aid in the preservation of the autophagy lysosomal system and mitigate oxidative stress in skeletal muscle during heart failure (HF) progression. Exercise tolerance was lower in HF groups compared to Control (C) groups ( p < 0.05). In skeletal muscle, HF induced type II fiber atrophy (type IIa: p = 0.0007; type IIx/b: p < 0.0001) and impaired all five oxidative phosphorylation complexes ( p < 0.05). Exercise reduced protein carbonyls ( p = 0.0043), while HF decreased antioxidant enzymes (manganese-superoxide dismutase: p = 0.0077; glutathione peroxidase: p = 0.0497) compared to C groups. HF elevated LC3B-II/I ratio compared to C ( p = 0.0246) and reduced cathepsin B ( p = 0.0484), consistent with altered autophagy, although autophagic flux was not assessed. Exercise lowered p62 expression ( p = 0.0449). WGCNA analysis identified an inverse correlation between MEbrown genes and autophagy-lysosomal markers. HF reduced aerobic capacity, likely due to mitochondrial impairments and reduced antioxidant defenses. Autophagy-related pathways remained partially responsive to exercise and may represent an adaptable component of muscle remodeling during HF progression.