γ-Tocotrienol attenuates oxidative stress and preserves mitochondrial function in inflammation-induced muscle atrophy

Muscle atrophy, marked by the loss of skeletal muscle mass and strength, presents a major health concern with diverse etiologies, including chronic inflammation. Effective interventions are urgently needed for its prevention and treatment. Although α-tocopherol, the most abundant form of vitamin E, is known for its antioxidant benefits in muscle health, γ-tocotrienol exhibits superior antioxidant and anti-inflammatory properties. This study investigates the protective effects of γ-tocotrienol against muscle atrophy and compares its efficacy with α-tocopherol. Muscle atrophy was induced in differentiated C2C12 myotubes using lipopolysaccharide (LPS), with vitamin E pre-treatment applied prior to LPS challenge. Myotube morphology, expression of atrophy-related markers, and underlying molecular pathways were examined through immunofluorescence, western blotting, and quantitative proteomics. LPS treatment induced significant myotube atrophy without affecting cell viability. Notably, γ-tocotrienol pre-treatment preserved myotube size and suppressed key atrophy markers, including the E3 ubiquitin ligases MuRF-1 and Fbxo32/Atrogin-1. Proteomic analysis quantified 5,371 proteins and revealed that γ-tocotrienol alleviated atrophy by enhancing extracellular matrix organization and attenuating oxidative stress and mitochondrial dysfunction. These protective effects were further confirmed in vivo, where γ-tocotrienol administration preserved muscle strength, suppressed pro-inflammatory signaling, and restored mitochondrial biogenesis in LPS-treated mice. Collectively, these findings demonstrate that γ-tocotrienol offers superior protection against muscle atrophy compared to α-tocopherol, highlighting its therapeutic potential for individuals at risk of muscle wasting.