Fig. 7
FXR-FGF15 and FXR-SHP regulated BA synthesis in alternative pathway. a Dominant BAs in liver and ileum of HFD fed mice gavaged with 225 mg/Kg/day theabrownin and 50 mg/Kg/day TCA, TCDCA, TUDCA respectively for 8 weeks. n = 8 individuals/group. b mRNA expression of ileal FXR, FGF15 and hepatic FXR, SHP and BA synthetic genes in HFD fed mice gavaged with 225 mg/Kg/day theabrownin and 50 mg/Kg/day TCA, TCDCA, TUDCA respectively for 8 weeks. n = 8 individuals/group. c Immunofluorescence staining of ileal FXR, FGF15 and hepatic FXR, SHP of HFD fed mice gavaged with 225 mg/Kg/day theabrownin and 50 mg/Kg/day TCA, TCDCA, TUDCA respectively for 8 weeks (scale bar, 50 μm). d Fifty micromole per liter of TCDCA and TUDCA inhibited protein expression of nuclear FXR in the human FHs 74 Int and L02 cell lines, and 50 μM of CDCA and TCA activated the expression of nuclear FXR in human FHs 74 Int and L02 cell lines and promoted expression of CYP27A1 and CYP7B1 in alternative pathway of bile acids synthesis. n = 3 individuals/group. e Immunofluorescence staining of FXR, FGF19 in FHs 74 Int cells supplied with 50 μM CDCA, CDCA coupled with 50 μM of TCDCA, CDCA coupled with 50 μM of TUDCA, and 50 μM of TCA for 24 h (scale bar, 100 μm). f Immunofluorescence staining of FXR, SHP in L02 cell lines supplied with 50 μM of CDCA, CDCA coupled with TCDCA, CDCA coupled with TUDCA and TCA for 24 h (scale bar, 50 μm). g The mRNA expression of ileal FXR, FGF15 and hepatic BA synthetic genes in HFD fed mice gavaged with 225 mg/Kg/day theabrownin, theabrownin coupled with 100 mg/Kg/day fexaramine for 8 weeks. n = 8 individuals/group. h The mRNA expression of ileal FXR, FGF15 and hepatic BA synthetic genes in HFD fed mice gavaged with 225 mg/Kg/day theabrownin, theabrownin coupled with 50 μg/Kg/day recombinant FGF19 protein by intraperitoneal injection for 8 weeks. n = 8 individuals/group. The mRNA expression was normalized to GAPDH. Protein expression was normalized by β-Actin or Lamin B1. Data were expressed as mean ± SEM. Differences between data were assessed by the Mann–Whitney U test, *p < 0.05, #p < 0.005
