高脂饲料诱导小鼠代谢综合征及对肠道发育、肝脏功能和肠道菌群的影响

High-fat diet induces metabolic syndrome in mice and its influence on intestinal development,liver function and intestinal microbiota

目的探究高脂饲料诱导小鼠代谢综合征的效果,以及对肠道发育、肝脏功能以及肠道菌群的影响。方法40只3周龄雄性C57BL/6J小鼠随机分为2组:空白对照组和高脂饲料组。适应性喂养一周后,高脂饲料组采用高脂饲料(脂肪供能比60%)饲喂,空白对照组采用普通饲料(脂肪供能比11%)饲喂,共计20周。每周测量小鼠体重,每月测量空腹血糖。实验末测定小鼠糖耐量,收集粪便,提取粪便DNA,实时荧光定量PCR和二代测序分析小鼠粪便双歧杆菌含量及肠道菌群组成。收集血清、脏器和内脏脂肪,测定小鼠肝脏、脾脏、胰腺脏器系数、脂体比及肠道长度,测定血清中血脂水平、肝功能指标、瘦素和脂联素水平,HE染色观察小鼠肝脏炎症状况,油红O染色观察肝脏脂肪浸润程度。结果长期高脂饲料干预后,C57BL/6J小鼠体重增加,空腹血糖、口服糖耐量、血脂水平、脂肪含量以及瘦素、脂联素水平升高(P<0.05);肝脏炎症状况及脂肪浸润程度增加,小鼠肠道长度降低(P<0.05);双歧杆菌属浓度降低(P<0.05),两歧双歧杆菌和角双歧杆菌浓度增加(P<0.05);肠道菌群ACE、Chao1、Simpson和Shannon指数下降(P<0.05),门水平上高脂饲料组厚壁菌门、变形菌门和脱铁杆菌门增加(P<0.05),拟杆菌门和疣微菌门减少(P<0.05),且厚壁菌门与拟杆菌门的比例显著上升。结论高脂饲料可诱导C57BL/6J小鼠出现代谢综合征,并引起小鼠肠道发育受损、肝脏组织及功能异常、肠道菌群多样性降低,群落结构向肥胖型转变。

OBJECTIVE To evaluate the possibility of high-fat diet to induce metabolic syndrome and to alter intestinal development,liver function and intestinal microbiotaof C57 BL/6 J mice.METHODS Total 40 of male C57 BL/6 J aged 3 weeks old were randomly divided into two groups:control group and high-fat diet group.After one week of adaptive feeding,the tested mice in high-fat diet group were fed with high-fat diet for 20 weeks,while those in control group were fed with ordinary diet.During the intervention,the body weight of the tested mice was measured weekly and fasting blood glucose(FBG)was measured monthly.Before the end of the experiment,the oral glucose tolerance test(OGTT)of the tested mice was conducted and the fecal 16 S rRNA sequencing was used to profile fecal microbiota of the test mice.Real-time qPCR was used to analyze the concentration of fecal bifidobacteria.Viscera coefficient of liver,spleen and pancreas,visceral fat-body ratio and intestinal length were measured.The indexes of liver function and the levels of serum lipids,leptin and adiponectin were also measured.Liver inflammation and fat infiltration were observed by anatomical pathological analysis.RESULTS After intervention of high fat diet,the body weight,FBG,oral glucose tolerance,the fat-body ratio,the levels of serum lipids,leptin and adiponectin of mice were significantly increased(P<0.05).The inflammatory state of liver and the degree of fat infiltration increased.The length of intestine decreased(P<0.05).The concentration of Bifidobacterium decreased(P<0.05),however,the concentration of B.bifidum and B.angulatum increased(P<0.05).The ACE,Chao1,Shannon and Simpson indexes of the high-fat diet were significantly lower than that of the control group(P<0.05).Firmicutes,Proteobacteria and Deferribacteres were found significantly more in high-fat diet group(P<0.05),while Bacteroidetes and Verrucomicrobia were apparently more in control group(P<0.05).CONCLUSION High-fat diet could induce the metabolic syndrome in tested C57 BL/6 J,and lead to the damage of intestinal development,abnormality of liver tissue and its function,decrease diversity of intestinal microbiota,and the transformation of intestinal microbiota community to obesity type.