摘要OBJECTIVE AMPK activator,act as exer-cise mimetics,effective in preventing or ameliorating met-abolic diseases,including obesity and diabetes.Systemic activating of AMPK represents an important therapeutic strategy to treat metabolic diseases.However,whether far-infrared(FIR)hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regu-lation,and its underling mechanisms remain unclear.METHODS The mice were subjected to hyperthermia in the FIR chamber(30±1)℃for 14 d.Exercise endurance was determined using a treadmill.Blood flow were mea-sured by the laser speckle contrast imaging.Combina-tion of microbiomic and metabolomic analysis,diversity of microbiota and metabolic profiling in muscle were detected.The microbiota disorder model via treatment with different cocktails of antibiotics(ABX).RESULTS The material characterization shows that the graphene synthesized by chemical vapour deposition(CVD)is dif-ferent from carbon fi ber,with single-layer structure and high electrothermal transform efficiency.The emission spectra generated by graphene-FIR device would maxi-mize matching those adsorbed by tissues(≈8.0 μm).Gra-phene-FIR improves core and epidermal temperature,and increases blood flow in femoral muscle and abdo-men.The diversity of gut microbiota was increased by graphene-FIR exposure.Graphene-FIR reduced the bac-teroidetes/firmicutes(B/F)ratio and increased the abun-dance of short-chain fatty acids(SCFA)-producing bac-teria,including Allobaculum,Blautia and Anaerostipes.Additionally,graphene-FIR stimulated the expression of SCFAs-sensing receptor(GPR 43),p-AMPK Thr172 and GLUT4,and increased the AMP/ATP ratio,thus enhanc-ing muscle glucose uptake.Metabolomic analyses revealed the significant changes in 25 metabolites,with twenty increased(eg.creatinine and phosphate)and five decreased(eg.lactic acid),and the marked impact of five metabolic pathways,including galactose metabo-lism,glycolysis,gluconeogenesis,fatty acid biosynthesis,butanoate metabolism,pyruvate metabolism.Further-more,a microbiota disorder model also demonstrates that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4.CON-CLUSION Our results provide convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis.These novel insights into graphene-FIR therapy suggest a potential as an exercise mimetic for the treatment of metabolic disease in clinical.