长期高脂饮食对糖脂代谢和焦虑样行为的影响

EFFECTS OF LONG-TERM HIGH-FAT DIET FEEDING ON GLUCOLIPID METABOLISM AND ANXIETY-LIKE BEHAVIORS IN MICE

目的 动态评估长期高脂饮食对C57BL/6J成年小鼠糖脂代谢和焦虑样行为的影响。方法 选用60只6~7 w龄健康雄性C57BL/6J小鼠,随机分为正常饮食(脂肪提供热量10%)实验组(NCD)和高脂饮食(脂肪提供热量60%)组(HFD),每组30只。各组又分为三个亚组,每个亚组10只,分别在设定饮食连续喂养2月、6月、9月后行胰岛素耐量试验(insulin tolerance test,ITT),并测量空腹血糖(fasting blood glucose,FBG)、空腹血胰岛素(fasting blood insulin,FBI)、血清甘油三酯(triglyceride,TG)和总胆固醇(total cholesterol,TC)水平,评价小鼠糖脂代谢;通过开放旷场实验(open field test,OFT)、高架零迷宫实验(elevated zero maze,EZM)评价小鼠焦虑样行为。结果 与同龄NCD小鼠相比,喂养2月后HFD小鼠FBG显著升高(P<0.01)、胰岛素耐量降低,行为学测试未见显著异常;喂养6月后,HFD小鼠进一步出现FBI显著增高(P<0.01),并出现焦虑水平显著增高(OFT:P<0.05;EZM:P<0.01);喂养9月后,HFD小鼠FBG仍显著高于同龄NCD组(P<0.01),而FBI升高已无显著性(P>0.05),同时血清TC水平显著增高(P<0.01),行为学实验显示焦虑水平持续增高(P<0.05)。结论 长期高脂饮食引起成年小鼠糖脂代谢功能受损,随着糖脂代谢损害的进行性加重,动物出现焦虑样行为。糖脂代谢损伤可能参与介导了高脂饮食促焦虑样行为效应。

Objective To dynamically evaluate the effects of long-term high-fat diet feeding on glucolipid metabolism and anxiety-like behaviors in adult C57BL/6J mice.Methods Healthy male C57BL/6J mice aged 6-7 weeks were selected and randomly divided into normal diet group(NCD) and high fat diet group(HFD).Each group was divided into three subgroups,and insulin tolerance test(ITT),fasting blood glucose(FBG),fasting blood insulin(FBI),triglyceride(TG) and total cholesterol(TC) were measured after feeding for 2 months,6 months and 9 months,respectively.Anxiety-like behaviors were evaluated by open field test(OFT) and elevated zero maze test(EZM).Results Compared with the NCD mice,FBG was increased significantly(P<0.01) and insulin tolerance decreased in HFD mice after 2 months of feeding,and there was no significant abnormality in behavioral test.After 6 months of feeding,FBI(P<0.01) and anxiety(OFT:P<0.05;EZM:P<0.01) level of HFD mice were further increased significantly.After 9 months of feeding,the FBG of HFD mice was still significantly higher than that of the NCD group(P<0.01),but the increase of FBI was not significant(P>0.05).At the same time,the level of serum TC was significantly increased(P<0.01),and the behavioral experiment showed that the level of anxiety was increased continuously(P<0.05).Conclusion Long-term HFD feeding impaired the function of glucolipid metabolism in adult mice.With the progressive aggravation of the disorder of occurrence of glucolipid metabolism,the animals showed anxiety-like behaviors.The damage of glucolipid metabolism may be involved in the occurrence of anxiety-like behaviors of HFD.