Metabolic Messengers: fibroblast growth factor 15/19
Metabolic Messengers: fibroblast growth factor 15/19
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DOI：
10.1038/s42255-019-0074-3
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发表时间：
2019-06-01
影响因子：
20.8
通讯作者：
Moschetta, Antonio
中科院分区：
文献类型：
--
作者：
Gadaleta, Raffaella Maria;Moschetta, Antonio
小鼠体内的成纤维细胞生长因子15及其人类同源基因FGF15/19(统称为FGF15/19)是一种肠道激素，在从进食到禁食状态的转变过程中控制胆汁酸和葡萄糖的动态平衡。FGF15/19除了在胆汁酸稳态调节中发挥核心作用外，现在被认为是肠道、肝脏、大脑和白色脂肪组织交叉点的横向代谢协调器。FGF15/19信号的失调可能导致几种影响肠道-肝轴的疾病和代谢性疾病的发生。在这里，我们提供了肠易激因子FGF15/19的生理作用的现有知识的概述，并强调了两个同源物之间的共同点和不同点。我们还讨论了在未得到满足的医疗需求领域的假定治疗潜力--例如胆汁淤积性肝病和非酒精性脂肪性肝炎，FGF19正在进行临床试验--以及使用FGF19治疗肥胖症和II型糖尿病的可能性。
Fibroblast growth factor (FGF) 15 in mice and its human orthologue FGF19 (together denoted FGF15/19) are gut hormones that control homeostasis of bile acids and glucose during the transition from the fed to the fasted state. Apart from its central role in the regulation of bile acid homeostasis, FGF15/19 is now recognized as a transversal metabolic coordinator at the crossroads of the gut, liver, brain and white adipose tissue. Dysregulation of FGF15/19 signalling may contribute to the pathogenesis of several diseases affecting the gut-liver axis and to metabolic diseases. Here, we provide an overview of current knowledge of the physiological roles of the enterokine FGF15/19 and highlight commonalities and differences between the two orthologues. We also discuss the putative therapeutic potential in areas of unmet medical need-such has cholestatic liver diseases and nonalcoholic steatohepatitis, for which FGF19 is being tested in ongoing clinical trials-as well as the possibility of using FGF19 for the treatment of obesity and type II diabetes.