DCo(H2)ding the Metabolic Functions of SIRT1 in the Intestine Philippe Lefebvre, Bart Staels  Gastroenterology  Volume 146, Issue 4, Pages 893-896 (April 2014) DOI: 10.1053/j.gastro.2014.02.020 Copyright © 2014 AGA Institute Terms and Conditions

Figure 1 The SIRT1/HNF1α/FXR-controlled enterohepatic cycle of bile acids. FXR expression levels are controlled by SIRT1 in hepatocytes and enterocytes. In enterocytes, FXR regulation occurs through the level of acetylation of the HNF1α dimerization partner DCoH2. Ileal Fgf15 expression is also regulated in a SIRT1-dependent manner, thereby affecting hepatic bile acid production through Cyp7a1 repression. In addition to regulating hepatic HNF1α DNA-binding activity, hepatic SIRT1 affects FXR and histone acetylation levels, which contributes to adequate bile acid metabolism regulation. Hepatic SIRT1 deficiency predisposes to cholesterol gallstone formation on a lithogenic diet, whereas intestinal SIRT1 deficiency decreases intestinal bile acid reabsorption and FGF15 release into the portal circulation, thus promoting increased hepatic bile acid synthesis and protecting the liver from injury on a lithogenic diet. Other transcriptional pathways contributing to bile acid homeostasis are displayed and further discussed in the text. Gastroenterology 2014 146, 893-896DOI: (10.1053/j.gastro.2014.02.020) Copyright © 2014 AGA Institute Terms and Conditions