| Objective: To investigate the effects on insulin sensitivity in peripheral tissue and endothelium dependent vasodilation after 28-week high-fat diet feeding in rats.Methods: 41 male Sprague-Dawley(SD) rats were randomly divided into 2 groups: the high-fat diet feeding group(HF group) and the normal control diet feeding group(NC group). After 28 weeks feeding, the following items were detected: (1) body weight, visceral tat weight. (2) tasting blood glucose(FBG), fasting insulin(FINS), fasting serum free fatty acids(FFA) and triglyceride(TG). (3) Insulin sensitivity (glucose infusion rate, GIR) was evaluated by euglycemic hyper-insulinemia clamp. (4) Each arotic ring was mounted in an organ bath system at standardized tension. After equilibration, rings were contracted with PGF2α, and then observed the response for relaxation of acetylcholine. Similar experiments were conducted with sodium nitroprusside as the vasorelaxing agent.Results: (1) High-fat diet feeding increased body weight and visceral fat weight of rats significantly. (2) Compared with the NC group, the levels of FBG and FiNS in the HF group were significantly higher. While serum FFA and TG concentration in the HF group was obviously higher also (p＜0.05). (3)The GIR during euglycemic hyperinsulinemia clamp in the HF group was significantly lower than in the NC group(3.60±1.2mg·min-1·kg-1 vs 11.94±1.7mg·min-1·kg-1, p＜0.01). (4) Compared with the NC group, the rate of endothelium-dependent vasodilation(EDV) in the HF group was significantly lower(81.3±3.1％vs 35.2±2.4％, p＜0.01), however non-endothelium-dependent vasodilation was not different between both groups (85.4±3.2％vs 72.3±2.2％, p＞0.05). (5) Correlation analysis showed that visceral fat weight, subcutaneous fat weight and serum FFA concentration were negatively related to GIR, while serum FFA concentration and the rate of EDV were negatively.Conclusion: High-fat diet feeding resulted in insulin resistance and impaired EDV in rats, which was associated with the elevation of serum FFA. Objective: To investigate the mechanisms of 28-week high-fat diet feeding on endothelium dependent vasodilation in rat aorta.Methods: 41 normal male SD rats, 8-week old, were randomly divided into 2 groups: a normal diet feeding group(NC, n=20), a high fat diet feeding group(HF, n=21). After 28 weeks feeding, the following items were detected: (1) the serum level of malondialdehyde(MDA), glutathione(GSH). (2) the serum level of C-reactive protein(CRP). (3) the serum level of soluble vascular cell adhesion molecule-1(sVCAM-1). (4) Evaluate the response of the arotic ring treated with acetylcholine and sodium nitroprusside.(5) The eNOSmRNA expression in vascular endothelium was analyzed by semi-quantitative reverse transcriptas(RT)-polymerase chain reaction(PCR).Results: (1) The serum level of MDA was significantly, higher in HF group than in NC group (26.63±5.0 vs 16.86±4.5nmol/ml, p＜0.01). In contrast, the serum level of GSH in HF group (84.78±21.0 vs 124.10±34.7mg/ml, p＜0.01); (2) The serum level of CRP in the HF group were higher than the NC group(p＜0.05). (3) The serum level of sVCAM-1 in the HF group was higher than the NC group (p＜0.05). (4) Compared with the NC group, the rate of endothelium-dependent vasodilation(EDV) in HF group was significantly lower(81.3±3.1％vs 35.2±2.4％, p＜0.01), however non-endothelium-dependent vasodilation was not different between both groups(85.4±3.2％vs 72.3±2.2％, p＞0.05). (5) The level of eNOS mRNA was decreased by approximately 34％in the HF group (p＜0.05).Conclusion: The present study indicated that there was endothilal dysfunction after 28-week high-fat diet feeding and high serum FFA level might reduce endothelial NO production, which might be secondary to inhibit eNOSmRNA expression. The mechanisms might relate to the increased oxidative stress and inflammation reaction caused by high serum FFA level.
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