成纤维细胞生长因子21在代谢性疾病中的研究进展

Research progress in fibroblast growth factor 21 in metabolic diseases

成纤维细胞生长因子21(FGF21)属于成纤维细胞生长因子(FGF)家族成员,分泌到血液后结合到成纤维细胞生长因子受体1(FGFR1)和受体辅助蛋白(KLB)激活下游FGFR1信号通路,从而作用于大脑、肝脏、脂肪、骨骼肌和胰岛等靶组织。FGF21具有降糖、降脂和减重的作用,以FGF21为靶点,针对代谢相关疾病非酒精性脂肪肝炎(NASH)进行了相关药物研发,在人体临床试验中效果显著,靶向激活FGF21/FGFR/KLB信号通路有望用于临床治疗代谢性疾病。FGF21类似物治疗NASH药物开发的临床效果和安全性还有待进一步验证。本文就FGF21在代谢性疾病方面的作用机制和研究现状以及相关临床药物的研究进展进行总结概述,为临床治疗提供参考。

Fibroblast growth factor 21(FGF21)is an atypical member of the fibroblast growth factor(FGF)superfamily and is secreted into blood to act mainly in target tissues,including brain,liver,adipose tissue,skeletal muscle and pancreas islet via a heterodimeric receptor complex comprising fibroblast growth factor receptor(FGFR1)and coreceptorβ-Klotho.Previous studies suggest that FGF21 can decrease blood glucose levels and body weight.Targeting FGF21 has emerged as an option for nonalcoholic steatohepatitis(NASH)therapy.The current clinical trials indicate that FGF21 has the potential for the treatment of nonalcoholic steatohepatitis.However,the effect of FGF21 analog on liver histology,clinical outcome and safety needs to be further verified with a larger number of patients.This review summarizes the mechanism and recent development of FGF21 functions in metabolic diseases and related clinical drug research advances,which might provide a suitable reference for clinical management.