| Objective: To observe the effect of micronised fenofibrate (Lipanthyl)on lipotoxicity and neointimal hyperplasia of SHR treated with high-fatdiet, and its possible mechanism.Methods: After balloon injury, twenty-seven SHR were randomly dividedinto three groups: normal chow group (n=9), high-fat diet group (n=9) andmicronised fenofibrate-treated group (n=9). Micronised fenofibrate 100mg.kg-1.day-1 was given orally to SHR which diet on high-fat diet for fourmonths. The nutrient composition of the fat diet expressed as a percentageof energy was as follows: 59% fat(mainly composed of lard), 21% protein,and 20% carbohydrate. The body weight and blood pressure was measuredmonthly. Glucose tolerance test was performed every two months. After fourmonths, soleus muscles were quickly obtained and stored in liquid nitrogenfor subsequent analysis of oil red O stain of cryostat sections.Intramuscular lipids were observed and lipids accumulation index(LAI) wascalculated. Serum triglyceride(TG), cholesterol)(TC), high densitylipoprotein-cholesterol (HDL-C), nonesterified fatty acid and insulinwere determined in all fasted rats. Abdominal artery was cannulatedimmediately for fixation of carotid artery. Image analysis system wasapplied to measure the area of lumina and the thickness of wall, and theratio of W to L was obtained.Results: (1) Comparing to SHR in normal chow diet group, body weight andthe level of serum TG and TC increased significantly and the level of HDL-Cdecreased significantly in SHR fed with high-fat diet (P < 0.05).Micronised fenofibrate significantly decreased systolic blood pressureand increased the level HDL-C (P﹤0.05). There was no difference betweenfenofibrate-treated group and normal chow diet group in body weight ,the level of serum TG and TC.(2) Fasted blood glucose, free fatty acid(FFA), GLU-AUC obviously increased in high-fat diet group compared withnormal chow diet group. Insulin sensitivity index(ISI) in high-fat dietgroup was much lower than that in normal chow diet group(0.0038±0.0007vs 0.0053 ±0.0013, P < 0.05 ) .No difference was found betweenfenofibrate-treated group and normal chow diet group.(3) W/L ratio ofcarotid artery on the control side had no significant difference amongthree groups. On the injured side, W/L ratio of carotid artery in high-fatdiet group was much thicker than that in normal chow group(0.36±0.03vs0.27±0.04,P<0.05)and local plaque was formed. No significantdifference was found between the W/L ratio of micronisedfenofibrate-treated group and that of normal chow diet group(P>0.05).(4) There were more lipid drops in intramuscular cells of SHR treated withhigh-fat diet than those in normal chow diet group(LAI: 6.42±0.59 vs1.98±0.97, P<0.05). Lipid drops in fenofibrate-treated group were almostthe same as those in normal chow diet group(LAI: 3.32±0.77 vs1.98±0.97,P>0.05). After covariance analysis, the results above-mentioned alsomade sense(F=10.46, P<0.05).(5)Inverse association was found betweenISI and LAI(r=-0.58, P<0.05).Conclusion: (1) Micronised fenofibrate may reduce the body weight,systolic blood pressure and the level of serum TG and TC of SHR, whileincrease the level of serum HDL-C.(2) Fenofibrate may reduce lipidaccumulation in intramuscular cells and improved insulin sensitivity ofSHR treated with high-fat diet. (3) It may also ameliorate the neointimalhyperplasia of balloon-injured carotid artery. Thus it may prevent thedevelopment of atherosclerosis. (4) There is an inverse associationbetween the amount of lipid contained within muscle fibers and insulinsensitivity.
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