Impact of Aerobic Training on Transcriptomic Changes in Skeletal Muscle of Rats with Cardiac Cachexia

Cardiac cachexia (CC) is an advanced stage of heart failure (HF) characterized by structural and functional abnormalities in skeletal muscle, leading to muscle loss. Aerobic training provides benefits; however, the underlying molecular mechanisms remain poorly understood. This study aimed to investigate the therapeutic effects of aerobic training on transcriptomic alterations associated with disease progression in cachectic skeletal muscle. HF was induced in male Wistar rats by a single monocrotaline injection (60 mg/Kg). Aerobic training consisted of 30 min treadmill running at ~55% of maximal capacity, 5×/week for 4 weeks. Assessments included body mass, right ventricle mass, skeletal muscle fiber size and exercise tolerance. RNA-seq analysis was performed on the medial gastrocnemius muscle. Sedentary cachectic rats exhibited 114 differentially expressed genes (DEGs) while exercised cachectic rats had only 18 DEGs. Enrichment pathways analyses and weighted gene co-expression network analysis (WGCNA) identified potential key genes involved in disrupted lipid metabolism in sedentary cachectic rats, which were not observed in the exercised cachectic rats. Validation of DEGs related to lipid metabolism confirmed that Dgat2 gene expression was modulated by aerobic training in CC rats. These findings suggest that aerobic training mitigates transcriptional alterations related to lipid metabolism in rats with CC, highlighting its therapeutic potential.