title: [Therapeutic effect of fibroblast growth factor 21 on hypertension induced by insulin resistance].
abstract: This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on hypertension induced by insulin resistance in rats and to provide mechanistic insights into its therapeutic effect. Male Sprague-Dawley (SD) rats were fed with high-fructose (10%) water to develop mild hypertensive models within 4 weeks, then randomized into 4 groups: model control, FGF21 0.25, 0.1 and 0.05 micromol x kg(-1) x d(-1) groups. Five age-matched normal SD rats administrated with saline were used as normal controls. The rats in each group were treated once a day for 4 weeks. Body weight was measured weekly, systolic blood pressure (SBP) was measured noninvasively using a tail-cuff method, insulin sensitivity was assessed using oral glucose tolerance test (OGTT) and HOMA-IR assay. At the end of the treatment, blood samples were collected, and blood glucose, serum cholesterol, serum triglyceride and serum insulin were measured. The results showed that blood pressure of the rats treated with different doses of FGF21 returned to normal levels [(122.2 +/- 3.5) mmHg, P < 0.01] after 4-week treatment, whereas, SBP of untreated (model control) rats maintained a high level [(142.5 +/- 4.5) mmHg] throughout the treatment. The observation of blood pressure in 24 h revealed that SBP of FGF21 treated-rats maintained at (130 +/- 4.5) mmHg vs. (143 +/- 5.5) mmHg for model control (P < 0.01). FGF21 treatment groups improved serum lipids obviously, total cholesterol (TC) and triglyceride (TG) levels decreased significantly to normal levels. The serum NO levels of three different doses FGF21 treatment group were significantly higher than that of the model control group [(7.32 +/- 0.11), (7.24 +/- 0.13), (6.94 +/- 0.08) vs. (6.56 +/- 0.19) micromol x L(-1), P < 0.01], and the degree of improvement showed obvious dose-dependent manner, indicating that FGF21 can significant increase serum NO in fructose-induced hypertension rat model and improve endothelial NO release function. The results of OGTT and HOMA-IR showed that insulin resistance state was significantly relieved in a dose-dependent manner. Thus, this study demonstrates that FGF21 significantly ameliorates blood pressure in fructose-induced hypertension model by relieving insulin resistance. This finding provides a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of essential hypertension.
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Sheng-long
authors.initials: SL
authors.lastname: Zhu
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Gui-ping
authors.initials: GP
authors.lastname: Ren
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Zhen-yu
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Wen-fei
authors.initials: WF
authors.lastname: Wang
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Xian-long
authors.initials: XL
authors.lastname: Ye
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Miao-miao
authors.initials: MM
authors.lastname: Han
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Jing-zhuang
authors.initials: JZ
authors.lastname: Zhao
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Tong-yu
authors.initials: TY
authors.lastname: Xu
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Ming-yao
authors.initials: MY
authors.lastname: Liu
authors.affiliation: College of Life Science, Northeast Agricultural University, Harbin 150030, China.
authors.forename: De-shan
authors.initials: DS
authors.lastname: Li
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005346:Fibroblast Growth Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D005632:Fructose; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D007333:Insulin Resistance; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D014280:Triglycerides; C414620:fibroblast growth factor 21; D005632:Fructose; D009569:Nitric Oxide; D005346:Fibroblast Growth Factors; D002784:Cholesterol