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.