Inhibition of a Novel CLK1-THRAP3-PPAR gamma Axis Improves Insulin Sensitivity

doi:10.3389/fphys.2021.699578

	Inhibition of a Novel CLK1-THRAP3-PPAR gamma Axis Improves Insulin Sensitivity
	Wang, Zhenguo 1,2; Gao, Xiaojing 2,3; Li, Qingrun 2; Zhu, Hongwen 2; Zhao, Xiangjie 1; Garcia-Barrio, Minerva 1; Zhang, Jifeng 1; Guo, Yanhong 1; Chen, Y. Eugene 1; Zeng, Rong2,4 ; Wu, Jia-Rui2,4 ; Chang, Lin 1
	2021-08-30
发表期刊	FRONTIERS IN PHYSIOLOGY (IF:3.2[JCR-2023],4.0[5-Year])
ISSN	1664-042X
卷号	12
DOI	10.3389/fphys.2021.699578
摘要	Increasing energy expenditure by promoting browning in adipose tissues is a promising strategy to prevent obesity and associated diabetes. To uncover potential targets of cold exposure, which induces energy expenditure, we performed phosphoproteomics profiling in brown adipose tissue of mice housed in mild cold environment at 16 & DEG;C. We identified CDC2-like kinase 1 (CLK1) as one of the kinases that were significantly downregulated by mild cold exposure. In addition, genetic knockout of CLK1 or chemical inhibition in mice ameliorated diet-induced obesity and insulin resistance at 22 & DEG;C. Through proteomics, we uncovered thyroid hormone receptor-associated protein 3 (THRAP3) as an interacting partner of CLK1, further confirmed by co-immunoprecipitation assays. We further demonstrated that CLK1 phosphorylates THRAP3 at Ser243, which is required for its regulatory interaction with phosphorylated peroxisome proliferator-activated receptor gamma (PPAR gamma), resulting in impaired adipose tissue browning and insulin sensitivity. These data suggest that CLK1 plays a critical role in controlling energy expenditure through the CLK1-THRAP3-PPAR gamma axis.
关键词	insulin sensitivity browning CLK1 THRAP3 PPAR gamma
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收录类别	SCIE
语种	英语
WOS研究方向	Physiology
WOS类目	Physiology
WOS记录号	WOS:000698517300001
出版者	FRONTIERS MEDIA SA
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/128248
专题	生命科学与技术学院_特聘教授组_曾嵘组生命科学与技术学院上海临床研究中心
通讯作者	Zeng, Rong; Wu, Jia-Rui; Chang, Lin
作者单位	1.Univ Michigan, Cardiovasc Ctr, Dept Internal Med, Med Ctr, Ann Arbor, MI 48109 USA; 2.Chinese Acad Sci, Univ Chinese Acad Sci, Hangzhou Inst Adv Study, CAS Key Lab Syst Biol, Hangzhou, Peoples R China; 3.Chinese Acad Sci, Univ Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol,Key Lab Syst Biol, Shanghai, Peoples R China; 4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Wang, Zhenguo,Gao, Xiaojing,Li, Qingrun,et al. Inhibition of a Novel CLK1-THRAP3-PPAR gamma Axis Improves Insulin Sensitivity[J]. FRONTIERS IN PHYSIOLOGY,2021,12.
APA	Wang, Zhenguo.,Gao, Xiaojing.,Li, Qingrun.,Zhu, Hongwen.,Zhao, Xiangjie.,...&Chang, Lin.(2021).Inhibition of a Novel CLK1-THRAP3-PPAR gamma Axis Improves Insulin Sensitivity.FRONTIERS IN PHYSIOLOGY,12.
MLA	Wang, Zhenguo,et al."Inhibition of a Novel CLK1-THRAP3-PPAR gamma Axis Improves Insulin Sensitivity".FRONTIERS IN PHYSIOLOGY 12(2021).