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 (60mg/Kg). Aerobic training consisted of treadmill running for 30min at ~55% of maximal capacity, 5x/week for 4 weeks. Assessments included body mass, right ventricle mass, skeletal muscle fiber size and exercise tolerance. RNA sequencing analysis was per-formed on the medial gastrocnemius muscle. Sedentary cachectic rats exhibited 114 differentially expressed genes (DEGs) while exercised cachectic rats had only 18 DEGs compared to their respective controls. GO enrichment, pathway enrichment, and weighted gene co-expression network analysis (WGCNA) identified key DEGs as po-tential hub genes involved in disrupted lipid metabolism and muscle remodeling in sedentary CC rats, which were not observed in the exercised CC rats. These findings suggest that aerobic training mitigates transcriptional alterations related to lipid me-tabolism and muscle remodeling in rats with CC, highlighting its therapeutic potential. RNA-seq profiling of medial gastrocnemius muscle from Sedentary cachectic rats, exercised cachectic rats compared to their respective controls.