5,7-Dimethoxyflavone Attenuates Obesity-Associated Muscle Atrophy via AMPK and PI3K/Akt Pathways in ob/ob mice

5,7-Dimethoxyflavone (DMF), a bioactive flavone derived from Kaempferia parviflora Wall. ex Baker, has been reported to exhibit anti-obesity and muscle-protective potential; however, its effects on obesity-related muscle dysfunction and the underlying mechanisms in a leptin-deficient model remain to be fully elucidated. This study investigated the dual effects of DMF, on obesity and muscle atrophy in ob/ob mice. Male ob/ob mice were randomly assigned to vehicle- or DMF (20 or 50 mg/kg/day)-treated groups and orally administered DMF for 8 weeks, with age-matched wild-type mice serving as controls. Adiposity, skeletal muscle mass, grip strength, treadmill exercise endurance, and related molecular signaling pathways were evaluated. DMF significantly decreased body weight, fat volume, and fat mass without affecting appetite, suggesting a potential shift in energy partitioning. Mechanistically, DMF was associated with reduced expression of adipogenic transcription factors and lipogenic enzymes by upregulating AMP-activated protein kinase in epididymal fat. Conversely, DMF markedly increased muscle fiber size and muscle mass, which resulted in enhanced muscle function, such as exercise endurance and grip strength. At the molecular level, DMF activated the phosphatidylinositol 3-kinase / protein kinase B pathway, subsequently stimulating the mammalian target of rapamycin pathway and the concomitant phosphorylation of forkhead box O3a. Mitochondrial biogenesis-related markers were also upregulated by DMF. Overall, DMF may serve as a potential functional agent to mitigate obesity-induced muscle loss by modulating metabolic and atrophic signaling pathways.