富含生育三烯酚的棕榈油对动脉粥样硬化小鼠糖代谢的影响

Effect of tocotrienol rich fraction of palm oil on glucose metabolism in atherosclerotic mice

目的探讨富含生育三烯酚的棕榈油(TRF)对动脉粥样硬化小鼠糖代谢的影响及其可能的作用机制。方法载脂蛋白E基因缺陷(ApoE-/-)小鼠分为模型对照组、TRF0.05%和0.2%(W/W)组。TRF均匀混于饲料中,各组饲料中添加10%(W/W)的脂肪和0.2%(W/W)的胆固醇诱导动脉粥样硬化的形成。小鼠经TRF处理12和14周后分别进行口服葡萄糖耐量实验(OGTT)和胰岛素耐量实验(ITT);用相应试剂盒检测血清中总胆固醇(TC)、甘油三酯(TG)、游离脂肪酸(FFA)和胰岛素的含量;实时荧光定量PCR分析白色脂肪组织(WAT)中过氧化物酶体增殖物激活受体γ(PPARγ)、脂联素和葡萄糖转运体4(Glut4)的mRNA水平;利用荧光素酶报告系统检测TRF对PPRAγ的激活作用。结果OGTT和ITT实验显示,在非禁食和禁食的情况下,TRF均能够降低ApoE-/-小鼠的血糖,改善胰岛素的敏感性;TRF组小鼠血清中TG和FFA的水平均低于模型对照组;在WAT中,与模型对照组相比,TRF0.2%组上调脂联素mRNA水平(1.73±0.32)倍,TRF0.05%和0.2%组分别增加Glut4mRNA水平(1.89±0.24)和(2.01±0.61)倍,PPARγmRNA水平没有改变。荧光素酶报告系统检测结果显示,TRF对PPARγ-配体结合结构域、PPARγ1和PPARγ2的激活作用分别是溶剂对照组的(2.7±0.2),(6.1±0.6)和(5.3±0.1)倍。结论TRF能够很好地改善动脉粥样硬化小鼠的糖代谢,TRF发挥这些作用的部分原因是通过激活PPARγ来实现的。

AIM To investigate the effect of tocotrienol rich fraction of palm oil（TRF） on glucose metabolism in atherosclerotic mice and the possible mechanism.METHODS Apolipoprotein E gene deficient（ApoE-/-） mice were divided into 3 groups as model control,TRF 0.05% and 0.2%（W/W） groups.10%（W/W） fat and 0.2%（W/W） cholesterol were added into the diets to induce atherosclerosis formation.Oral glucose tolerance test and insulin tolerance test were conducted after mice were treated by TRF for 12 and 14 weeks respectively.Serum cholesterol,triglyceride,free fatty acid,and insulin levels were measured using corresponding kits.The mRNA expression levels for peroxisome proliferator-activated receptor γ（PPARγ）,adiponectin and glucose transporter 4（Glut4） in white adipose tissue（WAT） were determined by using quantitative real-time PCR.Activation of PPARγ by TRF was tested using luciferase reporter assays.RESULTS Compared with the model control group,TRF decreased non-fasting or fasting blood glucose levels and improved insulin sensitivity of ApoE-/-mice.Both TRF groups showed decreased levels of triglyceride and free fatty acid.The mRNA level of adiponectin in WAT was up-regulated by（1.73±0.32） times in TRF 0.2% group compared with the control group.Glut4 mRNA level was increased（1.89±0.24） and（2.01±0.61） times compared with control group in TRF 0.05% group and TRF 0.2% group respectively.The fold inductions of TRF on PPARγ-ligand-binding domain,PPARγ1 and PPARγ2 activities were（2.7±0.2）,（6.1±0.65） and（5.3±0.1） times compared with DMSO by using luciferase reporter assay.CONCLUSION TRF can improve glucose metabolism in atherosclerotic mice and this effect may be partly due to modulating the activity of PPARγ.