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.