成纤维细胞生长因子21在非酒精性脂肪性肝病中的应用现状与展望

Current status and perspectives of fibroblast growth factor 21 in nonalcoholic fatty liver disease

成纤维细胞生长因子21(FGF21)是一种主要由肝细胞产生的分泌因子,在维持机体能量代谢平衡、调节胰岛素敏感性等过程中发挥重要作用。临床研究显示,血液FGF21在肥胖相关的非酒精性脂肪性肝病(NAFLD)患者中明显升高,是预测NAFLD发生发展的可靠生物标志物。在动物模型及NAFLD患者中,注射外源性FGF21可明显缓解该病病理进程。从FGF21的生物学特性出发,阐述其调控肝代谢及减轻肝损伤的分子作用机制,并着重讨论FGF21类似物及其受体激动剂在临床试验治疗NAFLD及非酒精性脂肪性肝炎的最新进展,以及遇到的主要问题与挑战,并展望其诊治NAFLD的应用前景。

Fibroblast growth factor 21(FGF21)is a peptide hormone predominantly secreted by the liver and plays a crucial role in maintaining whole-body energy metabolism and regulating insulin sensitivity.A large number of clinical studies have demonstrated that serum FGF21 levels are increased in obese patients with non-alcoholic fatty liver disease(NAFLD),and high circulating FGF21 is a sensitive biomarker for predicting the onset and progression of NAFLD.Injection of exogenous FGF21 can effectively alleviate pathological process in both animal models and NAFLD patients.This review aims to describe the molecular mechanism underlying the hepatoprotective effects of FGF21;to summarize the current data and challenges of the clinical trials on FGF21 analogs and receptor agonists in the treatment of NAFLD and nonalcoholic steatohepatitis(NASH);and to speculate the future directions of FGF21 as a diagnosis and treatment for NAFLD.