A new metabolic activity for oncogenic hormone FGF19

The hormone Fibroblast Growth Factor 19 (FGF19) has multiple metabolic functions, and is considered as a promising therapeutic target for chronic liver diseases. On the other hand, FGF19 has oncogenic functions in several cancers, notably hepatocellular carcinoma (HCC), the most frequent primary liver cancer. Because of these paradoxical effects on metabolism and oncogenesis, it is therefore crucial to better delineate the complex interplay of FGF19 roles and actions. In this work, led by Damien Grégoire, hydrodynamic gene transfer was used to generate a transgenic mouse model with hepatic overexpression of FGF19. Ursic-Bedoya, Chavey et al. identified a novel function of FGF19, namely the stimulation of water intake, via signaling in the central nervous system. HCC patients with elevated levels of circulating FGF19 have reduced serum sodium, indicating dipsogenic features. This work identifies a new activity of FGF19, which could be clinically relevant in the context of cancers overexpressing FGF19 and during the treatment of metabolic disorders by FGF19 analogues, currently in clinical development.

Ursic-Bedoya J.*, Chavey C.*, Meunier L., Desandré G., Dupuy AM., Gonzalez-Dopeso Reyes I., Tordjmann T., Assenat E., Hibner U., Grégoire D. (2022) The hormone Fibroblast Growth Factor 19 stimulates water intake. Molecular Metabolism, 2022, 60, 101483;