Ophiopogon japonicus Root Extract Attenuates Obesity-Induced Muscle Atrophy Through Regulation of the PI3K-AKT-mTOR/FoxO3a Signaling Pathway and Lipid Metabolism in Mice and C2C12 Myotubes

<b>Background:</b> Obesity-associated skeletal muscle atrophy is characterized by reduced muscle mass with excessive adipose accumulation, and there is no approved pharmacological therapy targeting both muscle anabolism and lipid metabolism. The root part of <i>Ophiopogon japonicus</i> (OJ), an edible traditional medicine (Liriopis seu Ophiopogonis Tuber), exhibits anti-diabetic, anti-inflammatory, and cardioprotective properties, yet its impact on obesity-associated muscle atrophy remains unknown. <b>Methods:</b> This study investigated the therapeutic potential and mechanisms of OJ extract against muscle atrophy in high-fat diet (HFD)-induced obesity mice and palmitate (PA)-stimulated C2C12 myotubes. <b>Results:</b> In obese mice, the administration of OJ extract inhibited muscle loss, improved muscle strength, and attenuated hepatic steatosis and dyslipidemia. Furthermore, OJ treatment restored myotube diameter, increased the expression of MyHC and Myogenin, and suppressed the expression of Atrogin-1 and MuRF1 in C2C12 myotubes. At the molecular level, OJ extract activated the PI3K-AKT-mTOR/FoxO3a signaling pathway and reprogrammed lipid metabolism in gastrocnemius tissues and myotubes. <b>Conclusions:</b> OJ extract alleviates obesity-induced muscle atrophy through regulation of the PI3K-AKT-mTOR/FoxO3a signaling pathway and lipid metabolism in muscle, indicating its potential as a natural therapeutic agent for obesity-associated muscle atrophy.