Fibroblast growth factor 21: a promising therapeutic target in obesity-related diseases.

Fibroblast growth factor 21 (FGF21) is a peptide hormone secreted by the liver, adipocytes, pancreas and skeletal muscle. It acts locally but is also a circulating hormone. Administration of FGF21 in animals and humans results in a decrease in body weight, blood triglycerides and LDL-cholesterol, with improvement in insulin sensitivity. FGF21 is known to play an important role during fasting and starvation by stimulating gluconeogenesis in the liver and inducing lipolysis in white adipose tissues. FGF21 expression is mediated by the peroxisome proliferator-activated receptor-α, while its biological actions are mediated through binding to a complex formed by its receptors and an essential coreceptor, β-Klotho. Serum FGF21 levels are paradoxically elevated in obesity, suggesting a decreased responsiveness. Recent data showed that serum FGF21 level is elevated in hypertension, atherosclerosis and coronary artery disease, raising the possibility that FGF21 plays a role in the pathophysiology of these diseases.