Author/Editor		Schmidt, Daniel R; Holmstrom, Sam R; Fon-Tacer, Klementina; Bookout, Angie L; Kliewer, Steven A; Mangelsdorf, David J
Title		Regulation of bile acid synthesis by fat-soluble vitamins A and D
Type		članek
Source		J Biol Chem
Vol. and No.		Letnik 285, št. 19
Publication year		2010
Volume		str. 14486-94
Language		eng
Abstract		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 elements appears 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 sequestrant cholestyramine 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 evolved as a means for these dietary vitamins to regulate their own absorption.
Descriptors		BILE ACIDS AND SALTS DIETARY FATS VITAMIN A VITAMIN D CYTOCHROME P-450 GENE EXPRESSION TRANSFECTION ILEUM POLYMERASE CHAIN REACTION PLASMIDS PROMOTER REGIONS (GENETICS) MICE, INBRED C57BL