Liu Wen-Yue, Xie Dong-Mei, Zhu Gui-Qi, Huang Gui-Qian, Lin Yi-Qian, Wang Li-Ren, Shi Ke-Qing, Hu Bin, Braddock Martin, Chen Yong-Ping, Zheng Ming-Hua
The First Affiliated Hospital of Wenzhou Medical University, Liver Research Center, Department of Infection and Liver Diseases , No. 2 Fuxue Lane, Wenzhou 325000 , China +86 577 88078232 ; +86 577 88078262 ;
Expert Opin Ther Targets. 2015 May;19(5):675-85. doi: 10.1517/14728222.2014.997711. Epub 2014 Dec 30.
Fibroblast growth factor 19 (FGF19) is a member of the hormone-like FGF family and has activity as an ileum-derived postprandial hormone. It shares high binding affinity with β-Klotho and together with the FGF receptor (FGFR) 4, is predominantly targeted to the liver. The main function of FGF19 in metabolism is the negative control of bile acid synthesis, promotion of glycogen synthesis, lipid metabolism and protein synthesis.
Drawing on in vitro and in vivo studies, this review discusses FGF19 and some underlying mechanisms of action of FGF19 as an endocrine hormone in several liver diseases. The molecular pathway of the FGF19-FGFR4 axis in non-alcoholic liver disease and hepatocellular carcinoma are discussed. Furthermore, definition of function and pharmacological effects of FGF19 for liver disease are also presented.
A series of studies have highlighted a crucial role of FGF19 in liver disease. However, the conclusions of these studies are partly paradoxical and controversial. An understanding of the underlying biological mechanisms which may explain inconsistent findings is especially important for consideration of potential biomarker strategies and an exploration of the putative therapeutic efficacy of FGF19 for human liver disease.
成纤维细胞生长因子19(FGF19)是类激素样成纤维细胞生长因子家族的成员,具有源自回肠的餐后激素活性。它与β-klotho具有高结合亲和力,并与成纤维细胞生长因子受体(FGFR)4一起,主要作用于肝脏。FGF19在代谢中的主要功能是对胆汁酸合成进行负调控、促进糖原合成、脂质代谢和蛋白质合成。
基于体外和体内研究,本综述讨论了FGF19以及FGF19作为内分泌激素在几种肝脏疾病中的一些潜在作用机制。讨论了非酒精性肝病和肝细胞癌中FGF19-FGFR4轴的分子途径。此外,还介绍了FGF19对肝病的功能定义和药理作用。
一系列研究突出了FGF19在肝病中的关键作用。然而,这些研究的结论部分存在矛盾且有争议。理解可能解释不一致结果的潜在生物学机制对于考虑潜在的生物标志物策略以及探索FGF19对人类肝病的假定治疗效果尤为重要。