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  2. 上海药物研究所
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A propolis-derived small molecule ameliorates metabolic syndrome in obese mice by targeting the CREB/CRTC2 transcriptional complex

文献类型：期刊论文

作者Chen, Yaqiong4; Wang, Jiang5,6; Wang, Yibing5,6,7; Wang, Pengfei7,8; Zhou, Zan7,8; Wu, Rong7,8; Xu, Qian9; You, Hanyun3; Liu, Yaxin4; Wang, Lei4
刊名NATURE COMMUNICATIONS
出版日期2022-01-11
卷号13期号:1页码:20
DOI10.1038/s41467-021-27533-9
通讯作者Hu, Lihong(lhhu@njucm.edu.cn) ; Liu, Hong(hliu@simm.ac.cn) ; Liu, Yi(liuyee@fudan.edu.cn)
英文摘要The molecular targets and mechanisms of propolis ameliorating metabolic syndrome are not fully understood. Here, we report that Brazilian green propolis reduces fasting blood glucose levels in obese mice by disrupting the formation of CREB/CRTC2 transcriptional complex, a key regulator of hepatic gluconeogenesis. Using a mammalian two-hybrid system based on CREB-CRTC2, we identify artepillin C (APC) from propolis as an inhibitor of CREB-CRTC2 interaction. Without apparent toxicity, APC protects mice from high fat diet-induced obesity, decreases fasting glucose levels, enhances insulin sensitivity and reduces lipid levels in the serum and liver by suppressing CREB/CRTC2-mediated both gluconeogenic and SREBP transcriptions. To develop more potential drugs from APC, we designed and found a novel compound, A57 that exhibits higher inhibitory activity on CREB-CRTC2 association and better capability of improving insulin sensitivity in obese animals, as compared with APC. In this work, our results indicate that CREB/CRTC2 is a suitable target for developing anti-metabolic syndrome drugs. Disruption of CREB/CRTC2, a key gluconeogenic transcriptional complex, has been shown to ameliorate insulin resistance in mice. Here, the authors show that the inhibitor artipllin C and the synthetic compound A57, which presents with higher inhibitory activity, improve insulin sensitivity in obese mice by inhibiting CREB-CRTC2 interaction.
WOS关键词ACID PHENETHYL ESTER ; PROMOTES INSULIN-RESISTANCE ; HEPATIC LIPID-METABOLISM ; LEUCINE ZIPPER PROTEIN ; CREB COACTIVATOR TORC2 ; X-RECEPTOR ; MODULATES GLUCONEOGENESIS ; BINDING PROTEIN ; ARTEPILLIN-C ; LIVER
资助项目National Key Research and Development Program[2021YFA08047] ; National Program on Key Basic Research Project of China 973 Program[NBR973] ; National Program on Key Basic Research Project of China 973 Program[2012CB524900] ; National Program on Key Basic Research Project of China 973 Program[2014CB910500] ; National Program on Key Basic Research Project of China 973 Program[2015CB910304] ; National Natural Science Foundation of China[NSFC 81390351] ; National Natural Science Foundation of China[31222028] ; National Natural Science Foundation of China[81620108027] ; National Natural Science Foundation of China[21632008] ; National Natural Science Foundation of China[31200891] ; National Natural Science Foundation of China[32171160] ; National Natural Science Foundation of China[21877118] ; Chinese Postdoctoral Science Foundation[20100480635] ; National Science & Technology Major Program[2013ZX09508104] ; Strategic Priority Program of Chinese Academy of Sciences and Technology[XDA12040306] ; Shanghai Municipal Science and Technology Major Project ; Program of Outstanding Scientific and Technological Innovation Team of Jiangsu Higher Education Institutions ; Priority Academic Program Development of Jiangsu Higher Education Institutions
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000741852200071
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/300433]  
专题新药研究国家重点实验室
通讯作者Hu, Lihong; Liu, Hong; Liu, Yi
作者单位1.Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China
2.Fudan Univ, MOE Frontiers Ctr Brain Sci, Sch Basic Med Sci, Shanghai 200032, Peoples R China
3.Nanjing Univ Chinese Med, Sch Pharm, Jiangsu Key Lab Funct Subst Chinese Med, Nanjing 210023, Peoples R China
4.Fudan Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Key Lab Metab & Mol Med,Minist Educ, Shanghai 200032, Peoples R China
5.Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
7.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
8.Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai 200031, Peoples R China
9.Harbin Med Univ, Dept Endocrinol, Affiliated Hosp 1, Harbin 150081, Heilongjiang, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Yaqiong,Wang, Jiang,Wang, Yibing,et al. A propolis-derived small molecule ameliorates metabolic syndrome in obese mice by targeting the CREB/CRTC2 transcriptional complex[J]. NATURE COMMUNICATIONS,2022,13(1):20.
APA Chen, Yaqiong.,Wang, Jiang.,Wang, Yibing.,Wang, Pengfei.,Zhou, Zan.,...&Liu, Yi.(2022).A propolis-derived small molecule ameliorates metabolic syndrome in obese mice by targeting the CREB/CRTC2 transcriptional complex.NATURE COMMUNICATIONS,13(1),20.
MLA Chen, Yaqiong,et al."A propolis-derived small molecule ameliorates metabolic syndrome in obese mice by targeting the CREB/CRTC2 transcriptional complex".NATURE COMMUNICATIONS 13.1(2022):20.

入库方式： OAI收割

来源：上海药物研究所

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