Portal bile acid perfusion bypasses ileal FGF19 and suppresses hepatic CYP7A1 expression in rabbits (605.6)

Abstract

This study challenged the hypothesis that CYP7A1 expression is regulated by a gut‐hepatic signaling pathway FGF15/19‐FGFR4 initiated from the ileum but not the liver. We would like to show that increase of portal bile acid flux alone should be able to suppress CYP7A1 expression. Methods: We developed a rabbit model to infuse glycodeoxycholic acid (GDCA) via the splenic vein to bypass ileal FGF19. Four study groups of rabbits (n=8/group): Control; bile fistula (BF); BF+GDCA (by portal perfusion); and BF+ GDCA‐f (by femoral perfusion). Results: Portal GDCA perfusion in the BF+GDCA group for 6 hours resulted in significant reduction in CYP7A1 mRNA but femoral perfusion in the BF+GDCA‐f group showed no change with the same perfusion rate of GDCA. In both GDCA perfusion groups, there was no increase in ileal FGF19 expression nor portal FGF19 protein levels, but similar increase in biliary bile acid outputs. Conclusions: This study demonstrated that portal bile acid flux alone inhibited CYP7A1 expression without increase of FGF19 in the ileum. However, the same bile acid flux through the liver via the hepatic artery (femoral perfusion) did not suppress the CYP7A1 expression. We propose that bile acid flux through the portal venous system may be the so called “intestinal factor” that suppresses CYP7A1 expression.Grant Funding Source: VA Merit Review Grant