Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France; Department of Hepatogastroenterology, Hepatology and Liver Transplantation Unit, Saint Eloi Hospital, University of Montpellier, France.
Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.
Mol Metab. 2022 Jun;60:101483. doi: 10.1016/j.molmet.2022.101483. Epub 2022 Mar 31.
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.
成纤维细胞生长因子 19（FGF19）是一种具有多种代谢功能的激素，这促使人们不断开发其类似物来治疗代谢紊乱。另一方面，FGF19 在一小部分肝细胞癌（HCC）患者中过表达，并具有致癌特性。因此，精确定义 FGF19 的作用至关重要，尤其是在慢性暴露于升高的激素浓度的情况下。在这里，我们使用水力基因转移生成了一种具有长期 FGF19 肝过表达的转基因小鼠模型。我们描述了 FGF19 的一种新作用，即刺激摄水量。这种表型至少持续 6 个月，依赖于中枢神经系统的信号传导，并且不依赖于 FGF21，尽管它模仿了其一些特征。我们还表明，循环 FGF19 水平高的 HCC 患者会出现低血钠症，表明存在口渴症状。本研究提供了 FGF19 新活性的证据，这在 FGF19 过表达癌症的情况下以及在使用 FGF19 类似物治疗代谢紊乱的过程中可能具有临床相关性。
