title: All-trans retinoic acid regulates hepatic bile acid homeostasis.
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.
authors.affiliation: Institute of Chinese Material Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cai-Lun Road, Shanghai 201203, China; Department of Pathology and Laboratory Medicine, the University of California at Davis Medical Center, 4645, 2nd Avenue, Sacramento, CA 95817, USA. Electronic address: fanyangforever@gmail.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pathology and Laboratory Medicine, the University of California at Davis Medical Center, 4645, 2nd Avenue, Sacramento, CA 95817, USA. Electronic address: hyqjeff@gmail.com.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Pathology and Laboratory Medicine, the University of California at Davis Medical Center, 4645, 2nd Avenue, Sacramento, CA 95817, USA. Electronic address: huixinliu2012@gmail.com.
authors.forename: Hui-Xin
authors.initials: HX
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, the University of California at Davis Medical Center, 4645, 2nd Avenue, Sacramento, CA 95817, USA. Electronic address: Jltsuei10@gmail.com.
authors.forename: Jessica
authors.initials: J
authors.lastname: Tsuei
authors.affiliation: Thermo Fisher Scientific, 355 River Oaks Pkwy, San Jose, CA 95134, USA. Electronic address: xiaoyue.jiang@thermofisher.com.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Institute of Chinese Material Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cai-Lun Road, Shanghai 201203, China. Electronic address: yangli7951@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Chinese Material Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cai-Lun Road, Shanghai 201203, China. Electronic address: wangzht@hotmail.com.
authors.forename: Zheng-Tao
authors.initials: ZT
authors.lastname: Wang
authors.affiliation: Institute of Chinese Material Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cai-Lun Road, Shanghai 201203, China; Department of Pathology and Laboratory Medicine, the University of California at Davis Medical Center, 4645, 2nd Avenue, Sacramento, CA 95817, USA. Electronic address: yjywan@ucdavis.edu.
authors.forename: Yu-Jui Yvonne
authors.initials: YJ
authors.lastname: Wan
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D001647:Bile Acids and Salts; D014212:Tretinoin
keywords: All-trans retinoic acid (Pubchem CID: 444795); CYP7A1; CYP8B1; FXR; Liver; Nuclear receptor; SHP