Regulation of bile acid synthesis by fat-soluble vitamins A and DSchmidt, Daniel R. ...Bile acids are required for proper absorption of dietary lipids, including fat-soluble vitamins. Here, we show that the dietary vitamins A and D inhibit bile acid synthesis by repressing hepatic ... expression of the rate-limiting enzyme, CYP7A1. Receptors for vitamin A and D induced expression of Fgf15, an intestine-derived hormone that acts on liver to inhibit Cyp7a1. These effects were mediated through distinct cis-acting response elements in the promoter and intron of Fgf15. Interestingly, trans-activation of both response elementsappears to be required to maintain basal Fgf15 expression levels in vivo. Furthermore, while induction of Fgf15 by vitamin D is mediated through its receptor (VDR), the induction of Fgf15 by vitamin A is mediated through the RXR/FXR heterodimer and is independent of bile acids, suggesting that the RXR/FXR heterodimer functions as a distinct dietary vitamin A sensor. Notably,vitamin A treatment reversed the effects of the bile acid sequestrantcholestyramine on Fgf15, Shp, and Cyp7a1 expression, suggesting a potential therapeutic benefit of vitamin A under conditions of bile acid malabsorption. These results reveal an unexpected link between the intake of fat-soluble vitamins A and D and bile acid metabolism, which may have evolvedas a means for these dietary vitamins to regulate their own absorption.Source: The Journal of biological chemistry. - ISSN 0021-9258 (Issue 19, Vol.285, 2010, str. 14486-14494)Type of material - article, component partPublish date - 2010Language - englishCOBISS.SI-ID - 26850777
Bile Acids And Salts | Metabolism | Dietary Fats | Vitamin A | Vitamin D | Cytochrome P-450 | Gene Expression | Transfection | Ileum | Enzymology | Polymerase Chain Reaction | Plasmids | Promoter Regions (Genetics) | Mice, Inbred C57bl | Citokrom P-450 | Vitamin A | Vitamin D | Žolčne kisline in soli | Dietne maščobe | Polimerazna, verižna reakcija | Gensko izražanje | Ileum | Miši seva C57BL | Plazmidi | Promoterska področja (genetika) | Transfekcija
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