组蛋白去甲基化酶抑制剂GSK-J4减轻高脂诱导的肥胖小鼠体质量

doi:10.16352/j.issn.1001-6325.2023.09.1353

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (9): 1353-1358.doi: 10.16352/j.issn.1001-6325.2023.09.1353

组蛋白去甲基化酶抑制剂GSK-J4减轻高脂诱导的肥胖小鼠体质量

陈辛^1,2, 陈俊^1,2, 徐幸^1,2, 王旭^1,2*

1.上海交通大学医学院附属第九人民医院口腔颌面-头颈肿瘤科,上海 200011;
2.上海交通大学口腔医学院国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所,上海市头颈肿瘤诊治和转化医学中心, 上海 200011

收稿日期:2023-04-11 修回日期:2023-07-12 出版日期:2023-09-05 发布日期:2023-09-01
通讯作者: ^*wangx312016@sh9hospital.org.cn
基金资助:
国家自然科学基金(81772886)

Histone demethylase inhibitor GSK-J4 reduces body weight in high-fat diet-induced obese mice

CHEN Xin^1,2, CHEN Jun^1,2, XU Xing^1,2, WANG Xu^1,2*

1. Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011;
2. National Center for Stomatology;National Clinical Research Center for Oral Disease;Shanghai Key Laboratory of Stomatology;Shanghai Research Institute of Stomatology; Shanghai Center of Head and Neck Oncology Clinicaland Translational Science, College of Stomatology, Shanghai Jiao Tong University, Shanghai 200011, China

Received:2023-04-11 Revised:2023-07-12 Online:2023-09-05 Published:2023-09-01
Contact: ^*wangx312016@sh9hospital.org.cn

摘要/Abstract

摘要： 目的研究组蛋白去甲基化酶抑制剂GSK-J4如何降低高脂诱导的肥胖小鼠体质量。方法使用高脂饲料(HFD)喂养C57/BL6小鼠16周后,连续腹腔注射GSK-J4 16 d,在此期间监测小鼠体质量和体温。ELISA试剂盒检测血清瘦素的表达。流式细胞测量术检测附睾和皮下脂肪组织中巨噬细胞的极化方向。HE染色和免疫组化的评价附睾脂肪组织和皮下脂肪组织中白色脂肪棕色化程度。RT-qPCR分析巨噬细胞中相关细胞因子和氧化磷酸化相关基因的表达水平。结果与溶剂对照组相比,GSK-J4时间依赖性降低小鼠体质量;显著降低血清中瘦素表达水平(P＜0.01);减少附睾和皮下脂肪组织巨噬细胞的表面标志物CD11c⁺减少;增加皮下白色脂肪棕色化程度;刺激棕色脂肪组织中氧化磷酸化相关基因mRNA水平表达,降低IL-1β表达水平。结论组蛋白去甲基化酶抑制剂GSK-J4可以减少巨噬细胞的M1极化。GSK-J4处理小鼠后可显著降低HFD所致肥胖小鼠的体质量,增加能量消耗。

关键词: 肥胖, 脂肪组织巨噬细胞, GSK-J4, 组蛋白去甲基化酶6

Abstract: Objective To investigate how histone demethylase inhibitor GSK-J4 could reduce body weight in obese mice fed high-fat diet(HFD). Methods After 16 weeks of feeding C57/BL6 mice with a HFD, GSK-J4 was injected intraperitoneally for 16 days, during which time the body weight and body temperature were monitored. The serum leptin expression was measured using ELISA kits. Direction of macrophage polarization in epididymis and subcutaneous adipose tissue was detected by flow cytometry. The browning degree of white fat in adipose tissue of epididymis and subcutaneous adipose tissue was evaluated by HE staining microscopy and immunohistochemistry.Quantitative PCR was used to analyze the levels of related cytokines and the expression levels of genes related to oxidative phosphorylation in macrophages. Results Compared with solvent control group, GSK-J4 reduced body weight in a time-dependent manner. Serum leptin expression was significantly decreased (P＜0.01); The surface marker CD11c⁺ decreased in epididymal and subcutaneous adipose tissue macrophages. The degree of browning of subcutaneous white fat was increased; The mRNA level of oxidative phosphorylation related genes was stimulated in brown adipose tissue, and the expression of IL-1β was decreased. Conclusions The histone demethylase inhibitor GSK-J4 can reduce M1 polarization of macrophages. After treatment with GSK-J4, the body weight of obese mice induced by HFD is significantly decreased and the energy consumption is increased.

Key words: obesity, adipose tissue macrophage, GSK-J4, histone lysine demethylases 6

中图分类号:

R339.6

陈辛, 陈俊, 徐幸, 王旭. 组蛋白去甲基化酶抑制剂GSK-J4减轻高脂诱导的肥胖小鼠体质量[J]. 基础医学与临床, 2023, 43(9): 1353-1358.

CHEN Xin, CHEN Jun, XU Xing, WANG Xu. Histone demethylase inhibitor GSK-J4 reduces body weight in high-fat diet-induced obese mice[J]. Basic & Clinical Medicine, 2023, 43(9): 1353-1358.

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组蛋白去甲基化酶抑制剂GSK-J4减轻高脂诱导的肥胖小鼠体质量

Histone demethylase inhibitor GSK-J4 reduces body weight in high-fat diet-induced obese mice

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