Nutlin-3a通过抑制CIDEC的表达调控小鼠脂肪功能

doi:10.16352/j.issn.1001-6325.2024.02.0154

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (2): 154-158.doi: 10.16352/j.issn.1001-6325.2024.02.0154

Nutlin-3a通过抑制CIDEC的表达调控小鼠脂肪功能

陈恩惠^1,2, 杨佳卉³, 赵微², 解相宏², 郭艳芳², 刘晓军², 闫莉^1*

中国医学科学院基础医学研究所北京协和医学院基础学院 1.病理生理学系;
2.重大疾病共性机制研究全国重点实验室,北京 100005;
3.山西医科大学基础医学院微生物学与免疫学教研室,山西太原 030001

收稿日期:2023-09-23 修回日期:2023-11-27 出版日期:2024-02-05 发布日期:2024-02-05
通讯作者: ^*yanli@ibms.pumc.edu.cn
基金资助:
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)

Nutlin-3a regulates mouse adipose function by inhibition of CIDEC expression

CHEN Enhui^1,2, YANG Jiahui³, ZHAO Wei², XIE Xianghong², GUO Yanfang², LIU Xiaojun², YAN Li^1*

1. Department of Pathophysiology;
2. State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005;
3. Department of Microbiology and Immunology,Basic Medicine College,Shanxi Medical University,Taiyuan 030001, China

Received:2023-09-23 Revised:2023-11-27 Online:2024-02-05 Published:2024-02-05
Contact: ^*yanli@ibms.pumc.edu.cn

摘要/Abstract

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。

关键词: Nutlin-3a, 脂肪代谢, 脂肪组织, 诱导细胞凋亡DFF45样效应因子C(CIDEC)

Abstract: 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.

Key words: Nutlin-3a, fat metabolism, adipose tissue, CIDEC

中图分类号:

R339.6

陈恩惠, 杨佳卉, 赵微, 解相宏, 郭艳芳, 刘晓军, 闫莉. Nutlin-3a通过抑制CIDEC的表达调控小鼠脂肪功能[J]. 基础医学与临床, 2024, 44(2): 154-158.

CHEN Enhui, YANG Jiahui, ZHAO Wei, XIE Xianghong, GUO Yanfang, LIU Xiaojun, YAN Li. Nutlin-3a regulates mouse adipose function by inhibition of CIDEC expression[J]. Basic & Clinical Medicine, 2024, 44(2): 154-158.

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Nutlin-3a通过抑制CIDEC的表达调控小鼠脂肪功能

Nutlin-3a regulates mouse adipose function by inhibition of CIDEC expression

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