1. All-trans retinoic acid regulates hepatic bile acid homeostasis.
- Author
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Yang, Fan, He, Yuqi, Liu, Hui-Xin, Tsuei, Jessica, Jiang, Xiaoyue, Yang, Li, Wang, Zheng-Tao, and Wan, Yu-Jui Yvonne
- Subjects
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TRETINOIN , *BILE acids , *HOMEOSTASIS , *INSULIN resistance , *RETINOID X receptors , *GENE expression , *MESSENGER RNA - Abstract
Retinoic acid (RA) and bile acids share common roles in regulating lipid homeostasis and insulin sensitivity. In addition, the receptor for RA (retinoid x receptor) is a permissive partner of the receptor for bile acids, farnesoid x receptor (FXR/NR1H4). Thus, RA can activate the FXR-mediated pathway as well. The current study was designed to understand the effect of all-trans RA on bile acid homeostasis. Mice were fed an all-trans RA-supplemented diet and the expression of 46 genes that participate in regulating bile acid homeostasis was studied. The data showed that all-trans RA has a profound effect in regulating genes involved in synthesis and transport of bile acids. All-trans RA treatment reduced the gene expression levels of Cyp7a1 , Cyp8b1 , and Akr1d1 , which are involved in bile acid synthesis. All-trans RA also decreased the hepatic mRNA levels of Lrh-1 (Nr5a2) and Hnf4α (Nr2a1), which positively regulate the gene expression of Cyp7a1 and Cyp8b1 . Moreover, all-trans RA induced the gene expression levels of negative regulators of bile acid synthesis including hepatic Fgfr4 , Fxr , and Shp (Nr0b2) as well as ileal Fgf15 . All-trans RA also decreased the expression of Abcb11 and Slc51b , which have a role in bile acid transport. Consistently, all-trans RA reduced hepatic bile acid levels and the ratio of CA/CDCA, as demonstrated by liquid chromatography-mass spectrometry. The data suggest that all-trans RA-induced SHP may contribute to the inhibition of CYP7A1 and CYP8B1, which in turn reduces bile acid synthesis and affects lipid absorption in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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