核受体REV-ERBα整合生物钟与能量代谢

doi:10.16288/j.yczz.22-310

遗传 ›› 2023, Vol. 45 ›› Issue (2): 99-114.doi: 10.16288/j.yczz.22-310

核受体REV-ERBα整合生物钟与能量代谢

冒姝羽¹(), 赵昌睿¹, 刘畅¹^,²()

1.中国药科大学生命科学与技术学院，南京 211198
2.重庆中国药科大学创新研究院，重庆 401135

收稿日期:2022-09-26 修回日期:2022-11-09 出版日期:2023-02-20 发布日期:2022-11-23
通讯作者: 刘畅，博士，教授，研究方向：生物钟与能量代谢。E-mail: changliu@cpu.edu.cn
作者简介:冒姝羽，在读硕士研究生，专业方向：细胞生物学。E-mail: 3220030438@stu.cpu.edu.cn
基金资助:
国家自然科学基金(92057112);国家重点研发计划(2021YFF0702000)

The nuclear receptor REV-ERBα integrates circadian clock and energy metabolism

Mao Shuyu¹(), Zhao Changrui¹, Liu Chang¹^,²()

1. School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
2. Chongqing Innovation Institute of China Pharmaceutical University, Chongqing 401135, China

Received:2022-09-26 Revised:2022-11-09 Published:2023-02-20 Online:2022-11-23
Supported by:
the National Natural Science Foundation of China(92057112);the National Key Research and Development Program of China(2021YFF0702000)

摘要/Abstract

摘要：

哺乳动物的各项生理活动以24 h为周期呈现节律性变化。稳定的昼夜节律由生物钟系统所精细调控，而昼夜节律的紊乱会导致代谢性疾病的发生。核受体超家族成员REV-ERBα是哺乳动物生物钟的重要组成部分，参与代谢、炎症、免疫和昼夜节律等多种生理过程的调节，是代谢性疾病、炎症性疾病和癌症的潜在治疗靶点。近年来发现了一系列新的REV-ERBα配体，其中大部分在疾病治疗方面具有潜在的应用价值。本文主要介绍核受体REV-ERBα在能量代谢以及炎症反应中的调节作用，以期为代谢综合征及相关疾病的治疗提供新的策略和参考。

本文勘误：见遗传, 2024, Vol. 46 (12): 1076.

关键词: REV-ERBα, 代谢, 炎症, REV-ERBα配体

Abstract:

The physiological processes of mammals show rhythmic changes in a 24-h cycle. Circadian rhythms are under the subtle control of the autonomous circadian clock, and dysregulation of the circadian system can lead to health problems such as metabolic disorders. REV-ERBα, a member of the nuclear receptor superfamily, is an important component of the mammalian circadian clock. REV-ERBα regulates various physiological processes, including the regulation of metabolism, inflammation and immunity as well as the circadian rhythm, making it a potential therapeutic target for metabolic syndrome, inflammatory diseases and cancers. In recent years, an array of new REV-ERBα ligands have been discovered, most of which have potential applications in the treatment of diseases. In this review, we focus on the regulatory role of nuclear receptor REV-ERBα in energy metabolism and inflammation, in order to provide new strategies for the therapy of metabolic syndrome and its related diseases.

Key words: REV-ERBα, metabolism, inflammation, REV-ERBα ligands

冒姝羽, 赵昌睿, 刘畅. 核受体REV-ERBα整合生物钟与能量代谢[J]. 遗传, 2023, 45(2): 99-114.

Mao Shuyu, Zhao Changrui, Liu Chang. The nuclear receptor REV-ERBα integrates circadian clock and energy metabolism[J]. Hereditas(Beijing), 2023, 45(2): 99-114.

图/表 5

表1

REV-ERBα在机体各组织中的功能"

组织	功能	疾病类型	参考文献
心脏	抑制CDKN1a/p21表达；增加心肌肌钙蛋白T释放	围手术期心肌损伤	[6]
	抑制NLRP3炎性小体激活；减少IL-1β、IL-18释放；减少巨噬细胞浸润	缺血再灌注损伤、心力衰竭	[7]
	维持脂肪酸氧化代谢；维持心脏收缩功能	扩张型心肌病、心力衰竭	[8]
	下调铁死亡/铁自噬；增强内源性心脏保护机制	缺血再灌注损伤	[9]
肺	减少CXCL1、CXCL2、CXCL5、G-CSF分泌；降低IL-6表达	肺部炎症	[10]
肺	抑制肌成纤维细胞激活；减少胶原分泌	肺纤维化	[11]
肝脏	抑制糖异生	糖尿病、血糖紊乱	[3,12]
	下调ApoC3、ApoA4水平；减少肝脏脂肪生成	高脂血症	[3,13~15]
	抑制胆汁酸合成	高胆固醇血症	[16,17,18,19]
	抑制同型半胱氨酸分解代谢；	高同型半胱氨酸血症	[20]
	抑制NLRP3炎性小体；减少IL-1β、IL-18释放	重型肝炎	[21]
胰腺	高糖情况下促进胰岛素分泌；低糖情况下促进胰高血糖素分泌；维持血糖稳态；提高β细胞功能与存活	血糖紊乱	[22,23,24,25]
结肠	抑制NF-κB信号传导；抑制NLRP3炎性小体；减少IL-1β表达	溃疡性结肠炎	[26]
结肠	增强肠道屏障功能；减少膳食脂肪吸收	肥胖、NASH	[27,28]
骨	抑制破骨细胞生成；减少破骨细胞骨吸收；减少伪足小体带形成；抑制骨生成	骨质疏松症	[29,30]
骨	减轻炎症反应；抑制M1型巨噬细胞极化；减少炎性细胞浸润；抑制NF-κB信号传导；抑制破骨细胞生成；减少活性氧的生成	类风湿性关节炎	[31]
大脑海马区	抑制NLRP3炎性小体激活；减少IL-1β、IL-18、IL-6及TNF-α表达；抑制星状细胞增多；抑制小胶质细胞增生	颞叶癫痫	[32]
大脑黑质纹状体	抑制NF-κB信号传导；抑制NLRP3炎性小体；减少IL-1β、IL-18、IL-6及TNF-α表达；促进M2型小胶质细胞极化	帕金森病	[33]
大脑	小胶质细胞吞噬作用；淀粉样蛋白β的清除	阿尔茨海默病	[34]
大脑	突触功能增加；突触数量增加；认知功能改善	阿尔茨海默病	[35]
肌肉	提高骨骼肌氧化能力；增加线粒体生物发生；下调自噬；提高骨骼肌运动功能；增加骨骼肌含量	杜氏肌营养不良症	[36,37,38]

表1

图1

图2

图3

图4

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核受体REV-ERBα整合生物钟与能量代谢

The nuclear receptor REV-ERBα integrates circadian clock and energy metabolism

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