FIG. 3.

The cardiometabolic protective pathway activated by CR. After CR, SIRT1 and AMPK are activated. SIRT1, through deacetylation, increases PGC-1α translocation to the nucleus and through binding to NRF2 activates the expression of HO-1 and UCP. Ultimately, CR attenuates the inflammatory response (by preventing NFκB activation), inhibits AKT overactivation, and reduces oxidative stress. Further, the reduction in ROS prevents the degradation of circulating adiponectin levels and through the adiponectin receptors the activation of this protective pathway is enhanced. AMPK, adenosine monophosphate-activated protein kinase; CR, caloric restriction; HO-1, heme oxygenase 1; NFκB, nuclear factor Kappa-light-chain-enhancer of activated B cells; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator-1α; SIRT, sirtuin; UCP, uncoupling protein. Color images are available online.