2026-04-05T10:53:12Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/511852025-11-19T20:40:43Zcom_2072_1057col_2072_478781col_2072_478917

00925njm 22002777a 4500 dc Langhi, Cédric author Pedraz Cuesta, Elena author Haro Bautista, Diego author Marrero González, Pedro F. author Rodríguez Rubio, Joan Carles author 2014-03-11T10:26:17Z 2014-03-11T10:26:17Z 2013-06-16 2014-03-11T10:26:18Z 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. Regulació genètica Alcohol Fetge Metabolisme Àcids biliars Genetic regulation Alcohol Liver Metabolism Bile acids Regulation of human class I alcohol dehydrogenases by bile acids