Comparing and Contrasting the Roles of AMPK and SIRT1 in Metabolic Tissues

Both SIRT1 and AMPK are activated by CR, starvation, exercise, and RSV. SRT1720 is a small molecule that specifically activates SIRT1, while AMPK is specifically activated by metformin and thiazolidinediones (TZDs). SIRT1 activation increases mitochondrial biogenesis and fatty acid oxidation through deacetylation and activation of PGC1-α. It is still not known yet whether PGC1-α induced expression of GLUT4 also requires SIRT1. Activated SIRT1 also blocks myogenesis, via MyoD and PCAF deacetylation.AMPK activation increases fatty acid oxidation acutely by direct phosphorylation of the enzymes ACC and MCAD, and chronically by phosphorylation and activation of PGC1-α, that is also required for AMPK mediated increase in mitochondrial biogenesis. AMPK controls glucose uptake by increased translocation of GLUT4 to the membrane and by increasing GLUT4 expression through PGC1-α activation. AMPK may also activate PGC1-α indirectly through SIRT1 activation via increase of Nampt expression, as described in the pathway that blocks myogenesis. AMPK activation induces also glycolysis.

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Comparing and Contrasting the Roles of AMPK and SIRT1 in Metabolic Tissues. () Marcella Fulco, et al. Cell Cycle. ;7(23):3669-3679. Figure: F1. All organisms Mus musculus Homo sapiens Drosophila melanogaster

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