Fig. 8: Schematic diagram of FGF21-mediated enhancement of endothelium-dependent relaxation.

The normal function of vascular endothelial cell is impaired by oxidative stress that is initiated by metabolic disorders. FGF21 binds to FGFRs (i.e., FGFR1) to potentiate CaMKK2 and AMPKα activities. On the one hand, AMPKα upregulates the expressions of CAT, Nrf-2 and HO-1 to abrogate oxidative stress. On the other hand, AMPKα directly enhances the activity of eNOS. The strengthened eNOS activity leads to an increased production of nitric oxide and restoration of endothelium-dependent vasodilatation