title: Mechanisms of enterohepatic fibroblast growth factor 15/19 signaling in health and disease.
abstract: The gut-derived hormone fibroblast growth factor 15/19 (FGF15/19) is an emerging versatile regulator of various metabolic pathways. As such, FGF15/19 has been implicated in homeostatic control of bile acid, carbohydrate and lipid metabolism in multiple target organs including the liver, adipose tissue and brain. In line with this, growing evidence suggests that dysregulation of FGF15/19 contributes to a number of metabolic and bile acid-associated disorders such as fatty liver disease, Type 2 diabetes and different gastrointestinal dysfunctions. In this review we summarize the current knowledge on the organ-specific functions of FGF15/19 and address their underlying molecular mechanisms. Moreover, recent advances in the characterization of factors that control the release of the hormone in the gut will be discussed and linked to the current view of how alterations of FGF15/19 signaling may contribute to disease development. Finally, the suitability of FGF15/19 as a potential therapeutic target will be critically reviewed.
authors.affiliation: University Hospital Würzburg (UKW), Division of Hepatology, Würzburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jahn
authors.affiliation: University Hospital Würzburg (UKW), Division of Hepatology, Würzburg, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Rau
authors.affiliation: University Hospital Würzburg (UKW), Division of Hepatology, Würzburg, Germany.
authors.forename: Heike M
authors.initials: HM
authors.lastname: Hermanns
authors.affiliation: University Hospital Würzburg (UKW), Division of Hepatology, Würzburg, Germany. Electronic address: Geier_A2@ukw.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Geier
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D009765:Obesity / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001647:Bile Acids and Salts; C117476:FGF19 protein, human; C108526:fibroblast growth factor 15, mouse; D005346:Fibroblast Growth Factors
keywords: Bile acid signaling; Energy metabolism; Fibroblast growth factor 15/19; Liver disease; Nuclear receptors; Obesity