高脂饮食诱导的内脏肥胖小鼠模型存在性别差异  

Sex discrepancy in establishing mouse visceral obesity model induced by high-fat diet

作　　者：彭晨芮 苗钟化 王一媚 程如越 沈曦 何方 PENG Chenrui;MIAO Zhonghua;WANG Yimei;CHENG Ruyue;SHEN Xi;HE Fang(West China School of Public Health and West China Fourth Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西公共卫生学院/华西第四医院,四川成都610041

出　　处：《浙江大学学报（医学版）》2023年第1期117-125,共9页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金(81973042)。

摘　　要：目的:比较不同性别BALB/c小鼠采用高脂饮食建立肥胖模型的差异。方法:32只4周龄无特定病原体级BALB/c小鼠(雌雄各半)随机分为雌性对照组、雌性高脂组、雄性对照组和雄性高脂组,每组8只。雌性对照组和雄性对照组采用普通饮食,雌性高脂组和雄性高脂组采用高脂饲料喂养,喂养12周后测量小鼠体重、内脏脂肪比、空腹血糖、葡萄糖耐量、血脂、代谢相关激素水平,并采用16S rRNA测序检测小鼠粪便菌群构成。结果:高脂饮食干预导致雄性小鼠体重和内脏脂肪比明显增加,病理表现为单个脂肪面积明显增大,肝脏脂肪滴堆积,总胆固醇、空腹血糖、口服糖耐量试验时间-血糖曲线下面积以及血清胰岛素水平明显上升(均P<0.05),并出现明显胰岛素抵抗(P<0.01)。而雌性高脂组体重、内脏脂肪比、血清胰岛素和瘦素水平与雌性对照组差异均无统计学意义(均P>0.05)。高脂干预后小鼠肥胖相关肠道菌群相对丰度显著变化并存在性别差异,其中雄性高脂组肥胖相关菌属(如布劳特菌)相对丰度明显增加,菌群结构变化更明显。结论:高脂饮食喂养12周4周龄BALB/c雄性小鼠可稳定建立以内脏脂肪堆积、代谢功能紊乱和肠道菌群变化为特点的内脏肥胖小鼠模型,而雌性小鼠高脂饮食诱导建立的肥胖模型这些特点不明显。Objective:To establish a mouse visceral obesity model,and to investigate the effect of animal sex on this model.Methods:Thirty-two 4-week-old BALB/c mice were randomly divided into female control group,female high-fat group,male control group and male high-fat group with 8 mice in each group.The control groups were given ordinary diet,and the high-fat groups were given high-fat diet.After 12 weeks of feeding,body weight,visceral fat,fasting blood glucose,glucose tolerance,blood lipid and metabolism-related hormone levels were measured,and the composition of gut microbiota of mice was analyzed by 16S rRNA sequencing.Results:The high fat diet resulted in a significant increase of body weight and visceral fat content in male mice;the pathological results showed significantly increased fat area,accumulation of liver fat droplets,increased total cholesterol,fasting blood glucose,oral glucose tolerance and serum insulin levels(all P<0.05),as well as significant insulin resistance(P<0.01).However,the above changes were not significant in female mice.Compared with the control groups,there was an increase in the relative abundance of obesity-related gut microbiota in the model groups(such as Blautia),and the microbiota structure changed significantly,while the changes were less obvious in female mice.Conclusion:A visceral obesity mouse model has been stably established by feeding high-fat diet in BALB/c male mice,showing visceral fat accumulation,metabolic dysfunction and gut microbiota changes;while female mice are not sensitive in this obesity model.

关 键 词：高脂饮食 内脏肥胖 性别 糖脂代谢 肠道菌群 小鼠 

分 类 号：R363.2[医药卫生—病理学] R589[医药卫生—基础医学]