EPA-enriched phospholipids and DHA-enriched phospholipids prevent dexamethasone-induced skeletal muscle atrophy via regulating protein turnover and mitochondrial quality.

The present study aimed to investigate the protective effects and underlying mechanisms of EPA-enriched phospholipids (EPA-PL) and DHA-enriched phospholipids (DHA-PL) against dexamethasone (DEX)-induced skeletal muscle atrophy both in vitro and in vivo. Results revealed that EPA-PL and DHA-PL significantly attenuated DEX-induced reduction in C2C12 myotube diameter. Additionally, supplementation with 1 % EPA-PL or 1 % DHA-PL for 6 weeks effectively alleviated DEX-induced declines in grip strength, skeletal muscle mass, and myofiber cross-sectional areas in mice. Data also manifested that EPA-PL and DHA-PL exerted strong roles on improving skeletal muscle protein turnover in DEX-treated mice, as evidenced by suppressing forkhead box O3a (FoxO3a)-mediated proteolysis, and enhancing protein synthesis via activation of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. Moreover, EPA-PL and DHA-PL notably reduced DEX-induced excessive reactive oxygen species accumulation and apoptosis in skeletal muscle, likely due to their ability to mitigate mitochondrial damage. The mechanisms underlying the attenuation of DEX-induced mitochondrial damage by EPA-PL and DHA-PL may be attributed to their role in improving mitochondrial quality through the regulation of molecular signals involved in mitochondrial biogenesis, dynamics, and mitophagy. Overall, EPA-PL and DHA-PL could serve as promising functional ingredients for preventing skeletal muscle atrophy.