Search

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]

Accumulation of hepatic lipid promotes systemic metabolic dysfunction and results in fatty liver. Our previous studies have shown that the alkaloids of Dendrobium nobile Lindl. (DNLA) could regulate the lipid metabolism gene expression in livers of mice. However, the protective effects on hepatic lipid homeostasis and the underlying mechanisms are still unclear. The C57BL/6 male mice were randomly divided into four groups, including control group, model group, DNLA treatment group, and simvastatin positive control group. Mice in the control group and the other three groups were fed with control diet and high fat diet during the full course of this study, respectively. Hepatic lipid accumulation was induced by HFD in mice after 18 weeks of feeding. DNLA (15 mg/kg) and simvastatin (20 mg/kg) were administrated intragastrically in the DNLA treatment group and simvastatin positive control group for another 18 weeks, respectively. HE staining and Oil-Red-O staining of liver tissues were observed. TC and TG levels in liver were assayed. The amount of major bile acids in mice livers were quantified by UPLC-MS. Expression levels of genes were tested by the real-time PCR. The results of HE staining and Oil-Red-O staining showed that DNLA could improve hepatic lipid homeostasis. DNLA significantly decreased liver TC and TG levels in the DNLA group. Moreover, the UPLC-MS analysis showed that DNLA did not only influence the hepatic bile acid quantity but did raise the hydrophilicity. Compared with the model group, DNLA decreased the hepatic levels of several free bile acids, including LCA, DCA, CA, and CDCA, and increased most important taurine-conjugated bile acids levels in liver, including TMCAs, TCDCA, TUDCA, and THDCA. In addition, DNLA also decreased the CA/CDCA ratio. The gene expression levels of Cyp27a1 , Cyp3a11 , Fxr , and Shp were up-regulated in DNLA treatment group. DNLA may improve the hepatic abnormal lipid profile of HFD-fed mice via two pathways: (1) enhancing the taurine-conjugated bile acids which are highly hydrophilic and contribute to the excretion of cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to cholesterol absorption. Image 1 [ABSTRACT FROM AUTHOR]