The vitamin D receptor (VDR) is a nuclear receptor for the active form of vitamin D3 and also for the secondary bile acid lithocholic acid (LCA). The in vivo role of VDR in bile acid metabolism remains largely uncharacterized. We previously reported that pharmacological VDR activation enhances urinary bile acid excretion, particularly in mice fed chow supplemented with chenodeoxycholic acid (CDCA), which is metabolized to muricholic acid in mouse liver and is also converted to LCA by intestinal bacteria. In this study, we examined the effect of VDR deletion on bile acid composition utilizing VDR-knockout (VDR-KO) mice. VDR deletion did not change total bile acid levels in liver or feces of mice when fed standard chow supplemented with calcium, needed to prevent hypocalcemia in VDR-KO mice. Total bile acid levels in plasma and urine tended to be higher and lower, respectively, in VDR-KO mice. After feeding CDCA-supplemented chow, VDR-KO mice showed decreased hepatic, fecal and urinary total bile acid and CDCA levels compared to wild-type mice. Plasma total bile acids and LCA were relatively high in these mice. These results indicate that VDR deletion influences CDCA metabolism. VDR may play a role in the excretion of excess bile acids.
Keywords: bile acid excretion; bile acid metabolism; lithocholic acid; nuclear receptor; vitamin D.