Modulation of Bile Acid Metabolism by 1α-Hydroxyvitamin D3 Administration in Mice

The vitamin D receptor (VDR) is a nuclear receptor for the active form of vitamin D₃ and mediates regulation of calcium homeostasis. Bile acids, such as lithocholic acid, have been identified as additional endogenous VDR ligands. The in vivo role of VDR in bile acid metabolism has not been elucidated. We investigated potential effects of in vivo VDR activation on bile acid metabolism by feeding mice bile acid-supplemented chow and then treating them with 1α-hydroxyvitamin D₃ [1α(OH)D₃]. We administered 1α(OH)D₃ via gavage to mice fed chow supplemented with 0.4% cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), or lithocholic acid (LCA) and examined liver and plasma bile acid composition with gas chromatography-mass spectrometry analysis. 1α(OH)D₃ treatment reduced hepatic bile acids in mice fed CDCA- and DCA-supplemented chow but was less effective in mice fed chow supplemented with LCA or CA. 1α(OH)D₃ administration also decreased plasma bile acids in mice fed bile acids, such as DCA. The effect of 1α(OH)D₃ administration in decreasing liver bile acid composition was observed in mice under fasting conditions and was associated with increased urinary excretion and increased expression of bile acid transporters, such as renal multidrug resistance-associated protein 4. These findings indicate that pharmacological activation of VDR enhances metabolism of bile acids, especially urinary excretion. The results confirm that VDR acts a regulator of bile acid metabolism in vivo.