The Enterokine Fibroblast Growth Factor 15/19 in Bile Acid Metabolism

Marica Cariello, Marilidia Piglionica, Raffaella Maria Gadaleta, Antonio Moschetta

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The endocrine fibroblast growth factors (FGFs), FGF19, FGF21, and FGF23, play a key role in whole-body homeostasis. In particular, FGF19 is a postprandial hormone regulating glucose homeostasis, glycogen and protein synthesis, and primary bile acid (BA) metabolism. In the ileum, BA-dependent farnesoid X receptor (FXR) activation induces the production of FGF19, which reaches the liver through the portal system where it represses the expression of CYP7A1, the rate-limiting enzyme of hepatic de novo BAs synthesis. Dysregulation of BA levels associated with alteration in FGF19 level has been depicted in different pathological conditions of the gut-liver axis. Furthermore, FGF19 exploits strong anti-cholestatic and anti-fibrotic activities in the liver. However, native FGF19 seems to retain peculiar hepatic pro-tumorigenic actions. Recently engineered FGF19 analogues have been recently synthetized, with fully retained BA regulatory activity but without intrinsic pro-tumoral action, thus opening bona fide novel pharmacological strategy for the treatment of gut-liver axis diseases.

Original languageEnglish
Title of host publicationHandbook of Experimental Pharmacology
PublisherSpringer New York LLC
Pages73-93
Number of pages21
DOIs
Publication statusPublished - Jan 1 2019

Publication series

NameHandbook of Experimental Pharmacology
Volume256
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

Keywords

  • Bile acid metabolism
  • Cholestasis
  • Fibroblast growth factors 19
  • Hepatocellular carcinoma

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

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