Fibroblast growth factor 19 stimulates water intake

• Published in: Molecular metabolism (Germany) 2022-06, Vol.60, p.101483-101483, Article 101483
• Main Authors: Ursic-Bedoya, José, Chavey, Carine, Desandré, Guillaume, Meunier, Lucy, Dupuy, Anne-Marie, Gonzalez-Dopeso Reyes, Iria, Tordjmann, Thierry, Assénat, Eric, Hibner, Urszula, Gregoire, Damien
• Format: Article
• Language: English
• Subjects: Animals; Brief Communication; Carcinoma, Hepatocellular - metabolism; Drinking; Endocrine; FGFR4; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Hepatocellular carcinoma; Hormones; Humans; Hydrodynamic gene transfer; Life Sciences; Liver; Liver Neoplasms - metabolism; Mice; Receptor, Fibroblast Growth Factor, Type 4 - genetics; Receptor, Fibroblast Growth Factor, Type 4 - metabolism
• ISSN: 2212-8778; 2212-8778
• DOI: 10.1016/j.molmet.2022.101483

Fibroblast growth factor 19 (FGF19) is a hormone with pleiotropic metabolic functions, leading to ongoing development of analogues for treatment of metabolic disorders. On the other hand, FGF19 is overexpressed in a sub-group of hepatocellular carcinoma (HCC) patients and has oncogenic properties. It is therefore crucial to precisely define FGF19 effects, notably in the context of chronic exposure to elevated concentrations of the hormone. Here, we used hydrodynamic gene transfer to generate a transgenic mouse model with long-term FGF19 hepatic overexpression. We describe a novel effect of FGF19, namely the stimulation of water intake. This phenotype, lasting at least over a 6-month period, depends on signaling in the central nervous system and is independent of FGF21, although it mimics some of its features. We further show that HCC patients with high levels of circulating FGF19 have a reduced natremia, indicating dipsogenic features. The present study provides evidence of a new activity of FGF19, which could be clinically relevant in the context of FGF19 overexpressing cancers and in the course of treatment of metabolic disorders by FGF19 analogues. [Display omitted] •Generation of a transgenic mouse model of overexpression of FGF19 by hepatocytes, at physiologically relevant levels.•Identification of a new metabolic activity of FGF19: stimulation of water consumption.•Hepatocellular carcinoma patients with high circulating levels of FGF19 display a reduced natremia.