title: Long-term high-fat diet links the regulation of the insulin-sensitizing fibroblast growth factor-21 and visfatin.
abstract: 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.
authors.affiliation: The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education, Chongqing Medical University, 400016 Chongqing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.forename: Gangyi
authors.initials: G
authors.lastname: Yang
authors.forename: Mengliu
authors.initials: M
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Guenther
authors.initials: G
authors.lastname: Boden
authors.forename: Ling
authors.initials: L
authors.lastname: Li
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D059305:Diet, High-Fat; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D001057:Apolipoproteins E; D001786:Blood Glucose; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D054409:Nicotinamide Phosphoribosyltransferase