Low-intensity resistance training with blood-flow restriction improves muscle function and activates amino acid and phospholipid metabolism in sarcopenia rat

Abstract Sarcopenia is an age-related disease characterized by progressive loss of muscle mass and strength, leading to functional decline and frailty. Although high-intensity resistance training effectively improves these disorders, it is often unsuitable for older or frail individuals. This study investigated whether low-intensity resistance training combined with blood-flow restriction improves muscle function, morphology, and metabolism in a rat model of sarcopenia induced by ovariectomy and dexamethasone. A total of 44 female rats were studied, including a normal control group (NC, n = 8) and four model-based groups: sarcopenia model (SM, n = 8), blood-flow restriction (BFR, n = 8), low-intensity resistance training (LI-RT, n = 10), and combined low-intensity resistance training with blood-flow restriction (LRB, n = 10). Metabolomic profiling based on combined criteria of VIP > 1.0, FDR q < 0.05, and fold change > 1.2 or < 0.83 identified 72, 102, and 119 differential metabolites in the NC vs. SM, SM vs. LRB, and NC vs. LRB comparisons, respectively, and revealed that treated rats exhibited a metabolic shift toward the healthy phenotype. After 8 weeks of intervention, functional assessments, histological analyses, and untargeted metabolomics were performed. LRB produced the greatest improvements in grip strength, rotarod performance, and muscle indices, and increased muscle-fiber size without changing fiber number, indicating hypertrophy. Metabolomic profiling further showed a shift toward a healthier metabolic phenotype, with changes in amino acid and phospholipid pathways, including arginine–proline, glycine–serine–threonine, and choline metabolism. These findings indicate that low-intensity resistance training combined with blood-flow restriction improves muscle strength and morphology in sarcopenia and may act through coordinated metabolic remodeling.