Ganoderic Acid A Enhances Glycometabolism in Mouse Gastrocnemius Muscle During Exercise-Induced Fatigue via...

Exercise-induced fatigue (EIF) is closely associated with impaired glycometabolism in skeletal muscle. This study investigated the protective effects of Ganoderic acid A (GAA) on glycometabolism in EIF mice and explored its underlying mechanisms. 60 KM mice were divided into five groups: a blank control (BC), a model control (MC), and three GAA-treated groups (20, 40, and 60 mg/kg/d). After a 7-week intervention, exhaustive treadmill tests and biochemical analyses were conducted to assess fatigue resistance, metabolic parameters, and molecular pathways. GAA administration significantly prolonged the exhaustive running time (p < 0.01), reduced serum levels of blood urea nitrogen (BUN), creatine kinase (CK), lactate dehydrogenase (LDH), and lactate (LD) (p < 0.05), and increased glycogen content in the liver and gastrocnemius muscle. Mechanistically, GAA increased AMPK phosphorylation, suggesting activation of the AMPK pathway, upregulated PGC-1α and GLUT4 expression, and enhanced succinate dehydrogenase (SDH) and Ca²⁺-Mg²⁺-ATPase activities. The results demonstrate that GAA alleviates EIF by enhancing energy metabolism through the AMPK/PGC-1α/GLUT4 pathway. These findings highlight GAA as a promising natural supplement for combating exercise-induced fatigue by improving glycometabolism.