Class I alcohol dehydrogenases (ADH1s) are the rate-limiting enzymes for ethanol 
and vitamin A (retinol) metabolism in the liver. Because previous studies have 
shown that human ADH1 enzymes may participate in bile acid metabolism, we 
investigated whether the bile acid-activated nuclear receptor farnesoid X 
receptor (FXR) regulates ADH1 genes. In human hepatocytes, both the endogenous 
FXR ligand chenodeoxycholic acid and synthetic FXR-specific agonist GW4064 
increased ADH1 mRNA, protein, and activity. Moreover, overexpression of a 
constitutively active form of FXR induced ADH1A and ADH1B expression, whereas 
silencing of FXR abolished the effects of FXR agonists on ADH1 expression and 
activity. Transient transfection studies and electrophoretic mobility shift 
assays revealed functional FXR response elements in the ADH1A and ADH1B proximal 
promoters, thus indicating that both genes are direct targets of FXR. These 
findings provide the first evidence for direct connection of bile acid signaling 
and alcohol metabolism.