Current understanding and controversies on the clinical implications of fibroblast growth factor 21

Metabolic functions of the hepatic hormone fibroblast growth factor 21 (FGF21) have been recognized for more than a decade in studying the responses of human subjects and rodent models to nutritional stresses such as fasting, high-fat diet or ketogenic diet consumption, and ethanol intake. Our interest in the beneficial metabolic effects of FGF21 has risen due to its potential ability to serve as a therapeutic agent for various metabolic disorders, including type 2 diabetes, obesity, and fatty liver diseases, as well as its potential to act as a diagnostic or prognostic biomarker for metabolic and other disorders. Here, we briefly review the FGF21 gene and protein structures, its expression pattern, and cellular signaling cascades that mediate FGF21 production and function. We mainly focus on discussing experimental and clinical literature pertaining to FGF21 as a therapeutic agent. Furthermore, we present several lines of investigation, including a few studies conducted by our team, suggesting that FGF21 expression and function can be regulated by dietary polyphenol interventions. Finally, we discuss the literature debating FGF21 as a potential biomarker in various disorders.