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Modulation of bile acid metabolism by 1alpha-hydroxyvitamin D3 administration in mice
Shigeru Nishida1, Jun Ozeki, Makoto Makishima
1Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan. maxima@med.nihon-u.ac.jp.
Abstract:
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.
Insights
Activating the vitamin D receptor (VDR) with 1alpha-hydroxyvitamin D(3) enhances bile acid metabolism in mice. This activation promotes increased urinary excretion of bile acids, confirming VDR
Area of Science:
- Endocrinology
- Hepatology
- Nutritional Science
Background:
- The vitamin D receptor (VDR) regulates calcium homeostasis and is activated by vitamin D.
- Bile acids, including lithocholic acid, are identified as endogenous VDR ligands.
- The in vivo function of VDR in bile acid metabolism remains largely uncharacterized.
Purpose of the Study:
- To investigate the in vivo effects of VDR activation on bile acid metabolism.
- To determine if pharmacological VDR activation influences liver and plasma bile acid composition.
- To explore the relationship between VDR activation and bile acid excretion pathways.
Main Methods:
- Mice were fed diets supplemented with various bile acids (cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid).
- Mice received 1alpha-hydroxyvitamin D(3) [1alpha(OH)D(3)] treatment via gavage.
- Liver and plasma bile acid profiles were analyzed using gas chromatography-mass spectrometry.
Main Results:
- 1alpha(OH)D(3) administration reduced hepatic bile acids in mice fed chenodeoxycholic acid and deoxycholic acid-supplemented chow.
- Plasma bile acid levels decreased in mice treated with 1alpha(OH)D(3) and fed deoxycholic acid.
- VDR activation was associated with increased urinary excretion and enhanced expression of bile acid transporters, particularly in fasting conditions.
Conclusions:
- Pharmacological activation of the VDR promotes bile acid metabolism, primarily through increased urinary excretion.
- The VDR plays a significant role in regulating bile acid metabolism in vivo.
- Targeting VDR may offer a therapeutic strategy for modulating bile acid homeostasis.
