高脂饮食对小鼠糖、脂代谢及肠道菌群结构的影响

EFFECTS OF HIGH-FAT DIET ON GLUCOSE AND LIPID METABOLISM AND GUT MICROBIOTA STRUCTURE IN MICE

目的探究高脂饮食对小鼠糖、脂代谢及肠道菌群结构的影响。方法 40只3 w龄C57BL/6雄性小鼠随机分为对照组和高脂组(n=20)。适应性喂养1 w后,对照组小鼠采用普通饲料喂养12 w,高脂组采用高脂饲料喂养12周。实验期间测量小鼠摄食量、体重与空腹血糖并收集粪便样本,实验结束时测量小鼠口服糖耐量并收集血清与内脏脂肪组织。采用全自动生化分析仪检测血清高密度脂蛋白、低密度脂蛋白、甘油三酯及总胆固醇含量,ELISA检测血清胰岛素、瘦素及脂联素含量并计算胰岛素抵抗指数,气相色谱法检测小鼠盲肠乙酸、丙酸及丁酸含量,16SrRNA测序技术分析肠道菌群结构。结果与对照组相比,高脂组小鼠平均每日摄食量及摄入能量升高(P<0.05),体重与内脏脂肪含量增加(P<0.05);空腹血糖增幅及血糖曲线下面积升高(P<0.05);血清高密度脂蛋白含量降低,低密度脂蛋白、甘油三酯、总胆固醇、瘦素及脂联素含量升高(P<0.05);盲肠乙酸、丙酸及丁酸含量显著降低(P<0.05);胰岛素抵抗指数无统计学差异(P>0.05);肠道菌群厚壁菌门相对丰度显著升高,拟杆菌门相对丰度显著降低(P<0.05);肠道菌群拟杆菌门另枝菌属(Alistipes)与Muribaculum属相对丰度降低(P<0.01);拟杆菌属(Bacteriodes)与Rikenella属相对丰度升高(P<0.01);厚壁菌门乳酸杆菌属(Lactobacillus)相对丰度降低(P<0.05);Intestinimonas属、肠球菌属(Enterococcus)(P<0.05)、Ruminiclostridium属、Tyzzerella属、乳球菌属(Lactococcus)、Oscillibacter属、Anearotruncus属与消化球菌属(Peptococcus)相对丰度升高(P<0.01);主成分分析显示两组群落结构存在显著差异(P<0.01)。结论高脂饮食可显著破坏小鼠血糖调节及脂质代谢能力并造成肠道菌群结构紊乱。[营养学,2020,42(5):458-464]

Objective This study aimed to explore the effects of high-fat diet on glucose and lipid metabolism and gut microbiota structure in mice.Methods Forty 3-week-old C57 BL/6 male mice were randomly divided into control group and high fat diet group(n=20/group).After one week of adaption,mice were fed with either normal chow or high-fat diet for 12 weeks.During the experiment,food intake,body weight and fasting blood glucose were measured daily and fecal samples were collected.After 12-week dietary intervention,oral glucose tolerance test was performed.Mice were euthanized and serum and visceral adipose tissues were collected.The contents of serum high density lipoprotein,low density lipoprotein,triglyceride and total cholesterol were detected by automatic biochemical analyzer.The contents of serum insulin,leptin and adiponectin were detected by ELISA and the homeostasis model assessment of insulin resistance(HOMA-IR index) was measured.The contents of acetic acid,propionic acid and butyric acid in cecum were detected by gas chromatgography.The gut microbiota structure was analyzed by 16 S rRNA sequencing technology.Results Compared with the control group,mice fed the high-fat diet significantly gained more body weight and visceral fat due to higher food and energy intake(P<0.05).and developed hyperinsulinemia,hyperglycemia,and hyperlipidemia.The contents of acetic acid,propionic acid and butyric acid in cecum were decreased(P<0.05).There was no significant difference between two groups in HOMA-IR index(P>0.05).The relative abundance of Firmicutes increased and Bacteroidetes decreased significantly(P<0.05).The relative abundance of Alistipe and Muribaculum decreased while Bacteriodes and Rikenella of Bacteroidetes increased(P<0.05).The relative abundance of Intestinimonas and Enterococcaceae(P<0.05),Ruminiclostridium,Tyzzerella,Lactococcus,Oscillibacter,Anearotruncus and Peptococcus of Firmicutes increased(P<0.01) while Lactobacillus decreased(P<0.05).Principal component analysis showed that there were significant differences in gut microbiota structure between the two groups(P<0.01).Conclusion High-fat diet can significantly impair blood glucose regulation and lipid metabolism in mice and cause gut microbiota structural disturbance.[ACTA NUTRIMENTA SINICA,2020,42(5):458-464]