Long-term high-fat diet links the regulation of the insulin-sensitizing fibroblast growth factor-21 and visfatin

High-fat diet (HFD) is associated with insulin resistance, hyperinsulinemia, elevated plasma free fatty acid (FFA), and increased risk for atherosclerotic vascular disease. However, the mechanisms underlying the HFD-induced insulin resistance have not been fully clarified. The aim of present study is to evaluate the effects of long-term HFD on the regulation of the insulin-sensitizing fibroblast growth factor-21 (FGF-21) and visfatin in ApoE−/− mice. A total of twenty male ApoE−/− mice were randomly divided into normal chow diet (NC) or HFD (HF) group for 16 weeks. Euglycemic–hyperinsulinemic clamp was performed to evaluate insulin sensitivity in this animal model. Both mRNA and protein contents of FGF-21 and visfatin were assayed by Quantitative real-time PCR and Western blot. Long-term HFD resulted in the marked abnormality of glucose and lipid metabolism as well as a large decrease in whole-body insulin sensitivity. Accompanied by abnormal glucose–lipid metabolism and aggravated insulin resistance, FGF-21, β-klotho, FGFR1, FGFR3 and FGFR4 mRNA expressions were markedly up-regulated, whereas visfatin mRNA expression was markedly down-regulated in liver and/or adipose tissue of HFD-fed mice. In addition, Western blotting also revealed both up-regulation of the FGF-21 protein and down-regulation of visfatin protein in liver, adipose tissue and plasma of HFD-fed mice. Both FGF-21 and visfatin expression and secretion are regulated by a potent regulator, long-term HFD. And these adipokines are associated with glucose–lipid metabolism and insulin resistance.

► High fat diet is associated with insulin resistance, hyperinsulinemia, increased risk for T2DM.
► The aim is to evaluate the effects of long term High fat diet in cytokine of FGF-21 and visfatin.
► FGF-21 and visfatin expression and secretion were regulated by a potent regulator, long-term HFD.
► The change of these cytokine was associated with glucose–lipid metabolism and insulin resistance.