The role of liver-derived fibroblast growth factor 21 in regulating glucose metabolism in mice

Abstract

Obesity and diabetes are becoming increasingly prevalent worldwide in the past ten years which can lead to life-threatening conditions such as Coronary Heart Diseases (CHDs) or atherosclerosis. FGF21 is an endocrine signalling protein found in vertebrates, predominantly expressed in liver, pancreas and white adipose tissue. It has high affinity with co-factor β-Klotho that mediates the ligand-receptor interaction with FGFR to signal for various metabolic processes by activating PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator-1-alpha). FGF21 is a novel potent therapeutic drug to treat metabolic syndromes since its pharmacological ability of improving metabolic symptoms including increase glucose tolerance, increase insulin sensitivity and resistance to diet induced weight gain have been widely studied and reported. FGF21 predominantly expressed in liver, pancreas and white adipose tissue. A few studies generated FGF21-deficient mice to elucidate the physiological effects of the protein. But the precise function of the FGF21 derived from the tissues mentioned about are remained unclear. In this study, we generated liver specific knockout of FGF21 to demonstrate the physiological role of hepatic FGF21 with glucose metabolism.