Figure 1.

NO signalling and metabolic syndrome-related pathways. ROS generated by NADPH oxidases and other sources (e.g. mitochondria, XO, uncoupled NOS, among others) leads to increased NF-κB activity followed by eNOS and iNOS up-regulation. eNOS produces NO which prevents activation of both NADPH oxidase and NF-κB. The leptin/STAT3 pathway may also up-regulate the gene for iNOS whereas the leptin/JAK2/IRS-1 pathway increases eNOS activity via Akt stimulation, as does insulin. Increased circulating free fatty acids lead to ceramide elevation with increasing effects on NADPH oxidase activity and diminishing effects on Akt activation. NO produced by neuronal NOS (nNOS) and putative mtNOS may affect heart function in metabolic syndrome by different specific routes.