Fibroblast growth factor 21 improves insulin resistance via inhibiting hepatic oxidative stress in obese mice / 西安交通大学学报(医学版)

ABSTRACT

Objective To explore the mechanism of insulin resistance regulated by fibroblast growth factor 21 (FGF21)and identify its role in oxidative stress.Methods High-fat diet-induced obese mice were treated with FGF21 ,and hepatic oxidative stress markers such as iNOS and insulin signaling molecules such as IRS-1 and Akt were assessed by Western blot and co-immunoprecipitation.Meanwhile,liver steatosis was assessed in liver sections stained with oil red O.Results Obese mice in FGF21 group showed reduced body weight,blood glucose and serum insulin levels,and improved insulin sensitivity as measured by glucose tolerance testing (GTT)and insulin tolerance testing (ITT)compared with obese mice in vehicle group.Meanwhile,FGF21 treatment in obese mice decreased protein expressions of iNOS and TNF-α,and increased insulin-stimulated IRS-1 tyrosine phosphorylation and Akt Ser-473 phosphorylation,indicating that FGF21 inhibited hepatic oxidative stress and restored impaired insulin signaling.Additionally,we found significantly reduced lipid accumulation in liver sections stained with oil red O in FGF21-treated obese mice.Conclusion Our results support the notion that FGF21 is an important regulator of insulin resistance and that FGF21 may reduce lipid accumulation in the liver,restore hepatic insulin signaling and improve insulin sensitivity in obese mice,at least in part,by inhibiting hepatic oxidative stress.Therefore,FGF21 has a potential value in clinical application.