Figure 2. SIRT1 regulates fatty acid oxidation and gluconeogenesis in the liver. Resveratrol, NAD+, fasting and calorie restriction activate SIRT1, causing deacetylation of PGC-1α, FOXO1, and TORC2 which in turn leads to increased fatty acid oxidation and gluconeogenesis. The exact mechanism underlying how SIRT1 activates PPARα and the precise role of PGC-1α in the SIRT1-mediated glucose homeostasis remain to be clarified.