摘要
目的探讨小鼠双微体同源基因2(MDM2)抑制剂Nutlin-3a对小鼠脂肪脂代谢功能的影响。方法建立C57BL/6J小鼠高脂饮食诱导肥胖(DIO)模型,随机分为对照组:腹腔注射DMSO,实验组:腹腔注射顺式咪唑啉类似物3a(Nutlin-3a)。实验期间进行葡萄糖耐量(GTT)以及胰岛素耐量(ITT)实验。实验结束后,分离小鼠附睾脂肪组织(eWAT)、皮下脂肪组织(iWAT)与棕色脂肪组织(BAT),对白色脂肪组织进行苏木精-伊红(HE)染色,观察脂肪细胞形态变化;RT-qPCR和Western blot检测eWAT中脂代谢相关基因表达。结果与对照组相比,给予小鼠Nutlin-3a处理,增加DIO小鼠的体质量(P<0.001);对葡萄糖耐量和胰岛素敏感性没有影响;脂肪细胞体积减小;下调白色脂肪中脂滴结合蛋白诱导细胞凋亡DFF45样效应因子C(CIDEC)的表达。结论Nutlin-3a通过下调白色脂肪组织中CIDEC的表达抑制脂滴的形成。
Objective To investigate the effect of Nutlin-3a,a mouse double minute 2 homolog(MDM2)inhibitor,on lipid metabolism of mouse adipose.Methods High-fat diet-induced obesity(DIO)C57BL/6J mice were randomly divided into a control group injected with DMSO and an experimental group injected with Nutlin-3a.Then we conducted glucose tolerance(GTT)and insulin tolerance(ITT)tests.The epididymal white adipose tissue(eWAT),inguinal white adipose tissue(iWAT)and brown adipose tissue(BAT)of animals were isolated and microscopy of WATs with hematoxylin-eosin(HE)staining was performed to observe the morphological changes of adipocytes.The expression of lipid metabolism related gene cell death-inducing DFF45-like effector C(CIDEC)in eWAT were detected by qPCR and Western blot.Results Compared with the control group,Nutlin-3a was found to promote the body weight(P<0.001),but no effect on glucose tolerance and insulin sensitivity in DIO mice.Nutlin-3a treatment decreased the size of adipocytes and fat deposition in adipose tissue and downregulated the mRNA and protein levels of CIDEC in eWAT.Conclusions Nutlin-3a inhibits the formation of lipid droplets by downregulating expression of CIDEC in white adipose tissue.
作者
陈恩惠
杨佳卉
赵微
解相宏
郭艳芳
刘晓军
闫莉
CHEN Enhui;YANG Jiahui;ZHAO Wei;XIE Xianghong;GUO Yanfang;LIU Xiaojun;YAN Li(Department of Pathophysiology,Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005;State Key Laboratory of Common Mechanism Research for Major Diseases,Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005;Department of Microbiology and Immunology,Basic Medicine College,Shanxi Medical University,Taiyuan 030001,China)
出处
《基础医学与临床》
2024年第2期154-158,共5页
Basic and Clinical Medicine
基金
国家重点研发计划(2022YFC2504002,2022YFC2504003)
中国医学科学院医学与健康科技创新工程(CIFMS2021-I2M-1-016)。
