Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of pathologies ranging from uncomplicated hepatic fat accumulation to a state of lobular inflammation and hepatocyte ballooning, known as non-alcoholic steatohepatitis (NASH). Currently, there are no reliable biomarkers or effective therapeutic options established for NAFLD. Nevertheless, there are several molecular targets in the pipeline, of which fibroblast growth factor 21 (FGF21) is one. FGF21 is secreted primarily from liver and has a plethora of metabolic functions. Pre-clinical and epidemiological studies indicate a relationship between circulating FGF21 levels and hepatic fat content in both mice and humans. Moreover, animal studies have clearly shown that aberrant FGF21 signalling is a key pathological step in the development and progression of NAFLD. A recent Phase II clinical trial demonstrated that administration of an FGF21 analogue significantly reduced hepatic fat in subjects with NASH. As such, FGF21 provides a novel target for future biomarker and therapeutic studies. This review appraises preclinical data to outline the current understanding of FGF21 function in both normal hepatic function and NAFLD. Epidemiological evidence is explored to delineate the relationship between circulating FGF21 levels and NAFLD in humans. Finally, we review the therapeutic effects of FGF21 in the treatment of NAFLD.

中文翻译：

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非酒精性脂肪肝中的成纤维细胞生长因子21。

非酒精性脂肪性肝病（NAFLD）涵盖了一系列病理，范围从简单的肝脂肪蓄积到小叶炎症和肝细胞膨胀的状态，被称为非酒精性脂肪性肝炎（NASH）。当前，对于NAFLD尚无可靠的生物标志物或有效的治疗选择。尽管如此，管线中仍存在一些分子靶标，其中成纤维细胞生长因子21（FGF21）是其中之一。FGF21主要从肝脏分泌，具有过多的代谢功能。临床前和流行病学研究表明，小鼠和人类的循环FGF21水平与肝脂肪含量之间存在相关性。此外，动物研究清楚地表明，异常的FGF21信号传导是NAFLD发生和发展的关键病理步骤。一项最近的II期临床试验表明，在患有NASH的受试者中，FGF21类似物的施用可显着减少肝脂肪。这样，FGF21为将来的生物标记和治疗研究提供了新的靶标。该评价评估临床前数据，以概述目前对正常肝功能和NAFLD中FGF21功能的理解。探索了流行病学证据来描述人体内循环FGF21水平与NAFLD之间的关系。最后，我们综述了FGF21在NAFLD治疗中的治疗作用。该评价评估临床前数据，以概述目前对正常肝功能和NAFLD中FGF21功能的理解。探索了流行病学证据来描述人体内循环FGF21水平与NAFLD之间的关系。最后，我们综述了FGF21在NAFLD治疗中的治疗作用。该评价评估临床前数据，以概述目前对正常肝功能和NAFLD中FGF21功能的理解。探索了流行病学证据来描述人体内循环FGF21水平与NAFLD之间的关系。最后，我们综述了FGF21在NAFLD治疗中的治疗作用。