Abstract
Nuclear receptors belonging to the NR1H and NR1I subfamilies, including vitamin D receptor (VDR, NR1I1), control cholesterol and bile acid metabolism. Bile acids are detergents essential for the digestion and intestinal absorption of hydrophobic nutrients, such as triacylglycerol, cholesterol and lipid-soluble vitamins, including vitamin D.Primary bile acids are generated from cholesterol and are secreted in bile as glycine and taurine conjugates. The intestinal microflora convert the primary bile acids to the secondary bile acids, including lithocholic acid (LCA). VDR, a receptor for 1,25-dihydroxyvitamin D_3(1,25(OH)_2D_3), acts as a bile acid receptor with specificity for the secondary bile acid LCA and its derivatives. VDR activation by 1,25(OH)_2D_3 or LCA induces the xenobiotic metabolism of bile acids. Synthetic LCA derivatives induce tissue VDR activation without inducing hypercalcemia in mice. VDR acts as a bile acid sensor as well as an endocrine receptor for vitamin D signaling.
