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Int. J. Mol. Sci. 2018, 19(7), 1975; https://doi.org/10.3390/ijms19071975

Lithocholic Acid Is a Vitamin D Receptor Ligand That Acts Preferentially in the Ileum

Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan
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Received: 26 May 2018 / Revised: 22 June 2018 / Accepted: 3 July 2018 / Published: 6 July 2018
(This article belongs to the Special Issue Molecular Biology of Nuclear Receptors)
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Abstract

The vitamin D receptor (VDR) is a nuclear receptor that mediates the biological action of the active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], and regulates calcium and bone metabolism. Lithocholic acid (LCA), which is a secondary bile acid produced by intestinal bacteria, acts as an additional physiological VDR ligand. Despite recent progress, however, the physiological function of the LCA−VDR axis remains unclear. In this study, in order to elucidate the differences in VDR action induced by 1,25(OH)2D3 and LCA, we compared their effect on the VDR target gene induction in the intestine of mice. While the oral administration of 1,25(OH)2D3 induced the Cyp24a1 expression effectively in the duodenum and jejunum, the LCA increased target gene expression in the ileum as effectively as 1,25(OH)2D3. 1,25(OH)2D3, but not LCA, increased the expression of the calcium transporter gene Trpv6 in the upper intestine, and increased the plasma calcium levels. Although LCA could induce an ileal Cyp24a1 expression as well as 1,25(OH)2D3, the oral LCA administration was not effective in the VDR target gene induction in the kidney. No effect of LCA on the ileal Cyp24a1 expression was observed in the VDR-null mice. Thus, the results indicate that LCA is a selective VDR ligand acting in the lower intestine, particularly the ileum. LCA may be a signaling molecule, which links intestinal bacteria and host VDR function. View Full-Text
Keywords: vitamin D receptor; vitamin D; lithocholic acid; bile acid; CYP24A1; TRPV6; calcium metabolism; ileum vitamin D receptor; vitamin D; lithocholic acid; bile acid; CYP24A1; TRPV6; calcium metabolism; ileum
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Ishizawa, M.; Akagi, D.; Makishima, M. Lithocholic Acid Is a Vitamin D Receptor Ligand That Acts Preferentially in the Ileum. Int. J. Mol. Sci. 2018, 19, 1975.

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