| Objective: To investigate the effects of fenofibrate,pioglitazone onVisfatin protein expression in SD rats.Methods: 120 6-wk-old male SD rats were divided into 2 groups randomly : NC group and HF group (n=60). NC group were fed with normal chow and the others with high-fat diets. After 12 weeks, models of obese rats were established, then the drug treated groups (NC + fenofibrate group, NC + pioglitazone group , HF + fenofibrate group and HF + pioglitazone group, n=20) were treated with 30mg/kg fenofibrate, 10mg/kg pioglitazone intragastric daily for 4 weeks, and the control groups with homologous solvent. The volume of drug or solvent was 2ml/kg daily. Body weight was measured regularly. Serum Visfatin,free fatty acids (FFA),triglyceride (TG),total cholesterol (TCH),fasting blood glucose (FBG) and fasting insulin (FINS) were detected after 16 weeks. Epididymis fat,kidney fat,omenta fat ( the three as visceral fat) and abdominal subcutaneous fat were weighed and harvested for protein extraction and western blot analysis. Gastrocnemius was also harvested for western blot and immunohistochemistry.Results (1) Compared with NC group , body weight (BW),visceral fat,subcutaneous fat,serum Visfatin,FBG,FINS,TG,FFA and HOMA-index of HF group were elevated significantly (P<0.05);but not TCH (P>0.05); BW,visceral fat,subcutaneous fat,serum Visfatin,FBG,FINS,TG,FFA,TCH and HOMA-index were not affected by fenofibrate or pioglitazone in the rats fed normal chow (P>0.05);Compared with HF group, BW,visceral fat,serum Visfatin,FBG,FINS,TG,FFA and HOMA-index were all downregulated in HF+fenofibrate group(P<0.05),but not subcutaneous fat or TCH (P >0.05);Serum Visfatin,FBG,FINS,TG,FFA and HOMA-index were decreased by pioglitazone in HF +pioglitazone group (P<0.05),and pioglitazone increased BW and subcutaneous fat (P<0.05) in high-fat diet fed SD rats but not visceral fat; (2) Visfatin was expressed widely in visceral fat,subcutaneous fat and muscle. Visfatin expression was much higher in visceral fat than subcutaneous fat than muscle in all of the rats. Additionally, there was no difference of Visfatin in subtaneous fat and muscle of different group animals (P>0.05). Fenofibrate and pioglitazone could downregulate visceral fat Visfatin in high-fat diets fed rats (P<0.05) but not subcutaneous fat or muscle (P>0.05). Both of the two drugs had no effect on Visfatin expression in the tissues of the animals fed normal chow. (3) Immunohistochemistry: in the muscle, Visfatin was expression in the muscle cells but not the interstitial tissue. (4) Correlation analysis: serum Visfatin was positively correlated with the weight of visceral fat,Visfatin expression in visceral fat,FBG,HOMA-index and TG.Conclusion: (1) High-fat diets could induced obesity in rats and metabolic disturbance of glucose and lipid; fenofibrate and pioglitazone could reduce lipid profiles and increase insulin sensitivity. Meanwhile, fenofibrate could reduce adiposity; both of the two drugs had no effects on metabolic disturbance of glucose and lipid in the animals of NC group. (2) Visfatin is an adipocytokine predominantly expressed in visceral fat and it could be detected in visceral fat,subcutaneous fat and muscle. (3) High-fat diets induced the rats to be obese with insulin resistance and the compensatory increase of Visfatin expressionl; fenofibrate and pioglitazone ameliorated the development of insulin resistance in HF-fed rats with a major decrease in Visfatin expression, the effects of pioglitazone and fenofibrate on Visfatin in HF-fed rats are secondary to changes in metabolic parameters; both of the two drugs had no effect on Visfatin expression in the rats of NC group; the mechanisms of the effects of fenofibrate and pioglitazone on Visfatin expression in the rats of different status await further investigation. |
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