Clinica Medica "Cesare Frugoni", Dipartimento Interdisciplinare di Medicina, Università degli studi di Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, Italy.
Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori "Giovanni Paolo II", Viale O. Flacco 65, 70124 Bari, Italy.
Nat Rev Drug Discov. 2016 Jan;15(1):51-69. doi: 10.1038/nrd.2015.9. Epub 2015 Nov 16.
The endocrine fibroblast growth factors (FGFs), FGF19, FGF21 and FGF23, are critical for maintaining whole-body homeostasis, with roles in bile acid, glucose and lipid metabolism, modulation of vitamin D and phosphate homeostasis and metabolic adaptation during fasting. Given these functions, the endocrine FGFs have therapeutic potential in a wide array of chronic human diseases, including obesity, type 2 diabetes, cancer, and kidney and cardiovascular disease. However, the safety and feasibility of chronic endocrine FGF administration has been challenged, and FGF analogues and mimetics are now being investigated. Here, we discuss current knowledge of the complex biology of the endocrine FGFs and assess how this may be harnessed therapeutically.
内分泌成纤维细胞生长因子(FGFs),包括 FGF19、FGF21 和 FGF23,对于维持全身内环境稳定至关重要,它们在胆汁酸、葡萄糖和脂质代谢、维生素 D 和磷酸盐稳态的调节以及禁食期间的代谢适应中发挥作用。鉴于这些功能,内分泌 FGF 在一系列广泛的慢性人类疾病中具有治疗潜力,包括肥胖症、2 型糖尿病、癌症以及肾脏和心血管疾病。然而,长期内分泌 FGF 给药的安全性和可行性一直受到挑战,目前正在研究 FGF 类似物和模拟物。在这里,我们讨论了内分泌 FGF 的复杂生物学的现有知识,并评估了如何将其用于治疗。