脂肪组织特异性染色体结构维持蛋白5基因敲除对小鼠糖脂代谢影响的研究  

Effect of adipocyte-specific Smc5 knockout on glucose and lipid metabolism

作　　者：施缘萍 叶伶[2] 金美玲[2] 朱文娇 SHI Yuanping;YE Ling;JIN Meiling;ZHU Wenjiao(Department of Endocrinology,Peking University People's Hospital,Beijing 100044,China)

机构地区：[1]北京大学人民医院内分泌科,100044 [2]复旦大学附属中山医院变态(过敏)反应科

出　　处：《中国糖尿病杂志》2024年第6期443-449,共7页Chinese Journal of Diabetes

基　　金：国家自然科学基金(82202054)。

摘　　要：目的探讨脂肪组织特异性染色体结构维持蛋白5(Smc5)基因敲除对小鼠糖脂代谢的影响。方法基于规律间隔成簇短回文重复序列及其相关核酸酶9(CRISPR/Cas9)系统构建脂肪组织Smc5特异性敲除(AKO)小鼠,以Smc5^(floxflox)纯合子小鼠(Flox小鼠)为对照。采用q RT-PCR和Western blot法验证小鼠脂肪组织Smc5敲除效率,双能X线吸收测量法(DEXA)检测小鼠体脂含量,苏木精-伊红染色观察小鼠脂肪组织形态并统计脂肪细胞面积分布。比较TG、HDL-C、LDL-C、FFA,腹腔注射葡萄糖耐量试验(IPGTT)和腹腔注射胰岛素耐量试验(IPITT)检测血糖。结果成功构建Smc5基因脂肪特异性敲除的AKO小鼠模型。AKO小鼠腹股沟脂肪(i WAT)、附睾脂肪(e WAT)和棕色脂肪细胞(BAT)中Smc5 mRNA、15周龄后体重、31周龄时i WAT脏器重量、e WAT脏器重量、BAT脏器重量、体重、脂肪量、脂肪量/体重、LDL-C、IPITT中15 min血糖较基线改变百分比低于Flox小鼠(P<0.05或P<0.01)。结论脂肪组织特异性Smc5基因敲除通过影响脂肪组织生成改善糖脂代谢。Objective To investigate the effectsof adipocyte-specific Structural maintenance of chromosomes 5(Smc5)knockouton glucose and lipid metabolism in mice.Methods Adipocyte-specific Smc5 knockout mice(AKO mice)were constructed based onclustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9(CRISPR/Cas9)systems,and Smc5~(floxflox)mice(Flox mice)were used as controls.The Smc5 knockout efficiency of adipose tissue in mice was verified by q RT-PCR and Western blot.The body fat content was detected by dual energy X-ray absorptiometry(DEXA).The morphology of adipose tissue was observed by hematoxylin-eosin staining and the area distribution of adipocytes was calculated.TG,HDL-C,LDL-C,free fatty acid(FFA),intraperitoneal glucose tolerance test(IPGTT)and intraperitoneal insulin tolerance test(IPITT)were compared.Results The AKO mouse model of fat specific knockout of Smc5 gene was successfully constructed.Smc5m RNA in groin fat(i WAT),epididymal fat(e WAT)and brown adipocyte(BAT)of AKO mice,body weight after 15 weeks,organ weight of iWAT at 31 weeks,organ weight of eWAT,organ weight of BAT,body weight,fat mass,fat mass/weight,LDL-C,and percentage of 15-minute blood glucose in IPITT were lower than those of Flox mice(P<0.05 or P<0.01).Conclusions Adipocyte-specific Smc5 gene knockout improves glucose and lipid metabolism by affecting adipose tissue production.

关 键 词：规律间隔成簇短回文重复序列及其相关核酸酶9 染色体结构维持蛋白5 小鼠 脂肪组织 血糖 

分 类 号：R587.2[医药卫生—内分泌]