Stevia Extract Improves Skeletal Muscle Metabolism and Mitochondrial Function While Attenuating Muscle Atrophy in Palmitate‐Treated C2C12 Myotubes and db / db Mice

Type 2 diabetes (T2DM) causes insulin resistance, fat accumulation, and mitochondrial dysfunction in skeletal muscle, leading to muscle atrophy and sarcopenia. This study investigated the effects of stevia extract (SE) on lipid metabolism, mitochondrial activity, and muscle atrophy in both cell and animal models of T2DM. C2C12 cells were treated with palmitic acid to induce insulin resistance, then exposed to different doses of SE (12.5-100 µg/mL). In addition, db/db mice were subjected to skeletal muscle analysis after administration of oral SE (200 or 500 mg/kg/day) for 35 days. SE treatment significantly reduced lipid accumulation and restored key anabolic signals, including AKT and mTOR. SE also upregulated mitochondrial regulators, AMPK, Sirt1, PGC-1α, PPARα, and FGF21 (p < 0.05-0.0001), while suppressing atrophy-associated genes Atrogin-1 and MuRF1 (p < 0.05-0.001). In db/db mice, oral SE (200 or 500 mg/kg) enhanced AMPK/Sirt1/PGC-1α signaling in gastrocnemius muscle and significantly reduced Atrogin-1 and MuRF1 expression (p < 0.05-0.01), indicating protection against muscle atrophy. These findings suggest that SE is a promising natural agent for preventing skeletal muscle deterioration in diabetic conditions.