The Enterokine Fibroblast Growth Factor 15/19 in Bile Acid Metabolism.
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.
['Cariello|Marica|M|', 'Piglionica|Marilidia|M|', 'Gadaleta|Raffaella Maria|RM|', 'Moschetta|Antonio|A|']
D001647:Bile Acids and Salts D000089703:Fibroblast Growth Factor-23 D005346:Fibroblast Growth Factors D006706:Homeostasis D006801:Humans D008099:Liver
Bile acid metabolism Cholestasis Fibroblast growth factors 19 Hepatocellular carcinoma