Fibroblast growth factor 21 in non-alcoholic fatty liver disease

• Published in: Metabolism, clinical and experimental clinical and experimental, 2019-12, Vol.101, p.153994-153994, Article 153994
• Main Authors: Tucker, Bradley, Li, Huating, Long, Xiaoxue, Rye, Kerry-Anne, Ong, Kwok Leung
• Format: Article
• Language: English
• Subjects: Animals; Chronic liver disease; Fibroblast growth factor-21; Fibroblast Growth Factors - blood; Fibroblast Growth Factors - physiology; Fibroblast Growth Factors - therapeutic use; Humans; Non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic steatohepatitis
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2019.153994

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. •FGF21 is a key regulator of hepatic glucose and lipid metabolism.•FGF21 resistance increases fatty acid supply to the liver and reduces fatty acid utilisation.•Hepatic fatty acid accumulation promotes lipotoxicity.•Circulating FGF21 levels are elevated in patients with NAFLD.•FGF21 mimetics are effective at reducing hepatic steatosis and inflammation.