Fibroblast growth factor 19 stimulates water intake
Résumé
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 subgroup 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.
Mots clés
Liver
FGFR4
Hepatocellular carcinoma
Hydrodynamic gene transfer
Endocrine FGF19
fibroblast growth factor 19
HCC
hepatocellular carcinoma
HGT
hydrodynamic gene transfer
FGFR
fibroblast growth factor receptor
FGF15
fibroblast growth factor 15
KLB
b-klotho
HPRT
hypoxanthine phospho-ribosyltransferase
SB100X
Sleeping Beauty transposase 100X
FXR
farnesoid X receptor
BCLC
Barcelona clinic liver cancer
Meld
Model for end stage liver disease
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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