Modulation of bile acid metabolism by 1alpha-hydroxyvitamin D3 administration in mice.
The vitamin D receptor (VDR) is a nuclear receptor for the active form of vitamin D(3) 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 1alpha-hydroxyvitamin D(3) [1alpha(OH)D(3)]. We administered 1alpha(OH)D(3) 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. 1alpha(OH)D(3) 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. 1alpha(OH)D(3) administration also decreased plasma bile acids in mice fed bile acids, such as DCA. The effect of 1alpha(OH)D(3) 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.
Nishida
Shigeru
S
Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan. maxima@med.nihon-u.ac.jp.
Ozeki
Jun
J
Makishima
Makoto
M
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002762:Cholecalciferol / Q000494:pharmacology*; D019826:Cholic Acid / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism*
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D002762:Cholecalciferol; D019826:Cholic Acid; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D018167:Receptors, Calcitriol