Since the discovery of the regulatory function of FGF21 in metabolism in 2005, studies have focused on the dramatic systemic pharmacological effects and clinical potential of FGF21 in alleviation of obesity and diabetes. These have obscured its general role as a stress hormone in organ-specific physiopathologies with adipose tissue as its tissue target and adipocyte FGFR1-KLB as its molecular target. The adipocyte FGFR1-KLB complex accounts for the weight reduction and anti-diabetic effects of pharmacological FGF21 (40–44). It also likely accounts for the stress-reducing metabolic effects of FGF21 in tissues undergoing a wide range of conditions causing systemic metabolic as well as local tissue and cellular stress. Induced FGF21 expression may be of utility as a biomarker for these conditions. In addition to obesity and its associated metabolic syndromes, pharmacological levels of FGF21 may be of therapeutic benefit for chronic tissue-specific stress-related diseases.
