The gut-liver axis in hepatocarcinoma: a focus on the nuclear receptor FXR and the enterokine FGF19

Current Opinion in Pharmacology
Marilidia PiglionicaAntonio Moschetta

Abstract

Elevated bile acid (BA) concentrations in the liver is associated with severe disease, including cholestasis and hepatocellular carcinoma. The nuclear Farnesoid X Receptor (FXR) is the master regulator of BAs homeostasis. In the ileum, BA-dependent FXR activation induces the production of the fibroblast growth factor FGF19, a hormone that reaches the liver through the portal system where it represses the expression of CYP7A1, the rate limiting enzyme in the process of hepatic BAs synthesis. This gut-liver FXR-FGF19 dual action is the paradigm of physiological BA regulation and it is currently targeted in the clinical practice for liver disease such as primary cholangitis. At a variance of FXR activation, native FGF19 has strong anti-cholestatic and anti-fibrotic activity in the liver but it retains peculiar pro-tumorigenic actions. Thus, novel analogues have been generated to avoid tumorigenic capacity while maintaining BA metabolic action. Here we present a novel and intriguing view on the putative possibility to target the FXR-FGF19 duo in order to offer a bona fide promising therapeutic approach to bile acid promoted hepatocarcinoma.

Citations

Jul 11, 2019·International Journal of Cancer. Journal International Du Cancer·Tianyu LiuHailong Cao
Jan 28, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·John Y L Chiang, Jessica M Ferrell
Aug 6, 2019·Frontiers in Endocrinology·Urša KovačTadeja Režen
Nov 19, 2019·International Journal of Endocrinology·Mengsiyu LiShuguang Pang
Feb 12, 2021·Nature Reviews. Gastroenterology & Hepatology·Raj VuppalanchiArun J Sanyal
May 18, 2021·The American Journal of Pathology·Zhongguang ChenJunyan Tao

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