The hormone Fibroblast Growth Factor 19 stimulates water intake

Abstract

Fibroblast growth factor 19 (FGF19) is a hormone with pleiotropic metabolic functions, leading to ongoing development of analogues for the 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 chronic exposure to elevated concentrations of the hormone. We used hydrodynamic gene transfer approach to generate a transgenic mouse model with long-term FGF19 hepatic overexpression. Here we describe a novel effect of FGF19, namely 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 dispogenic features. The present study provides evidence of a new activity for FGF19, which could be clinically relevant in the context of FGF19 overexpressing cancers and treatment of metabolic disorders by FGF19 analogues.