Figure 1.

Schematic representation of the actions of SIRT1 in liver, based on genetically engineered mouse models. Through direct deacetylation, SIRT1 enhances the transcriptional activity of a series of regulators, such as PGC-1α, the FOXO family of transcription factors, and the Liver X Receptor (LXR) or the Farnesoid X receptor (FXR). However, a series of other transcriptional regulators, such as SREBP-1c and CRTC2 are downregulated through deacetylation by SIRT1. Overall, SIRT1 activation favors lipid catabolism vs. anabolism, leading to protection against oxidative stress and sustainable glucose production during prolonged fasting.