Characterization of individual bile acids in vivo utilizing a novel low bile acid mouse model

• DOI: 10.1093/toxsci/kfae029
• Publication Date: 2024-03-25T13:47:48Z
• Authors: Rulaiha Taylor; Zhenning Yang; Zakiyah Henry; Gina Capece; Vik Meadows; Katherine Otersen; Veronia Basaly; Anisha Bhattacharya; Stephanie Mera; Peihong Zhou; Laurie Joseph; Ill Yang; Anita Brinker; Brian Buckley; Bo Kong; Grace L Guo
• Keywords: Farnesoid X receptor; Ursodeoxycholic acid; Deoxycholic acid; CYP27A1; Enterohepatic circulation; Chenodeoxycholic acid; Lithocholic acid; FGF19; Homeostasis; Hepatoprotection

Abstract Bile acids (BAs) are signaling molecules synthesized in the liver initially by CYP7A1 and CYP27A1 classical alternative pathways, respectively. BAs essential for cholesterol clearance, intestinal absorption of lipids, endogenous modulators farnesoid x receptor (FXR). FXR is critical maintaining BA homeostasis gut-liver crosstalk. Complex reactions vivo lack suitable animal models impede our understanding functions individual BAs. In this study, we characterized effects three-day feeding cholic acid (CA), deoxycholic (DCA), or ursodeoxycholic (UDCA) at physiological/non-hepatotoxic concentrations a novel low-BA mouse model (Cyp7a1−/−/Cyp27a1−/−, DKO). Liver injury, levels composition FXR-fibroblast growth factor 15 (FGF15) axis were determined. Overall, higher basal inflammation altered lipid metabolism DKO mice might be associated with low CA, DCA, UDCA activated signals tissue specificity. Dietary CA DCA similarly profiles to less hydrophobic, while promoted more hydrophobic pool shifted toward non-12α-OH secondary However, did not offer any overt protective as expected. These findings allow us determine precise on BA-FXR overall physiology pathologies.