Screening of FDA-approved drugs identifies sutent as a modulator of UCP1 expression in brown adipose tissue
文献类型：期刊论文
| 作者 | Qiu, Yan4; Sun, Yingmin4; Yang, Yuanyuan4; Liu, Xiaojian4; Wei, Yuda4; Chen, Yanhao4; Feng, Zhuanghui4; Li, Shuang4; Reyad-ul Ferdous, Md4; Zhao, Yongxu4 |
| 刊名 | EBIOMEDICINE
 |
| 出版日期 | 2018 |
| 卷号 | 37期号:-页码:344-355 |
| 关键词 | Uncoupling protein 1 Brown adipose FDA-approved drug library Obesity Sutent |
| ISSN号 | 2352-3964 |
| DOI | 10.1016/j.ebiom.2018.10.019 |
| 文献子类 | Article |
| 英文摘要 | Background: The pharmacological activation of thermogenesis in brown adipose tissue has long been considered promising strategies to treat obesity. However, identification of safe and effective agents remains a challenge. In this study, we addressed this challenge by developing a cellular system with a fluorescence readout, and applied in a high-throughput manner to screen for FDA-approved drugs that may activate endogenous UCP1 expression in adipocytes. Methods: We have generated a Ucp1-2A-GFP reporter mouse, in which GFP intensity serves as a surrogate of the endogenous expression level of UCP1 protein; and immortalized brown adipocytes were derived from this mouse model and applied in drug screening. Candidate drugs were further tested in mouse models either fed with normal chow or high fat diet to induce obesity. Findings: By using the cellular screening platform, we identified a group of FDA-approved drugs that can upregulate UCP1 expression in brown adipocyte, including previously known UCP1 activators and new candidate drugs. Further studies focusing on a previously unreported drug-sutent, revealed that sutent treatment could increase the energy expenditure and inhibit lipid synthesis in mouse adipose and liver tissues, resulting in improved metabolism and resistance to obesity. Interpretation: This study offered an easy-to-use cellular screening system for UCP1 activators, and provided a candidate list of FDA-approved drugs that can potentially treat obesity. Further study of these candidates may shed new light on the drug discovery towards obesity. (C) 2018 The Authors. Published by Elsevier B.V. |
| 学科主题 | General & Internal Medicine ; Research & Experimental Medicine |
| WOS关键词 | ACTIVATED PROTEIN-KINASE ; P38 MAP KINASE ; RETINOIC-ACID ; PPAR-GAMMA ; INDUCED THERMOGENESIS ; SUNITINIB MALATE ; BEIGE FAT ; ADIPOCYTES ; OBESITY ; GENE |
| 语种 | 英语 |
| WOS记录号 | WOS:000451691900047 |
| 出版者 | ELSEVIER SCIENCE BV |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/799]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China, 2.Shanghai Univ Tradit Chinese Med, Sch Pharma, Shanghai 201203, Peoples R China; 3.Shanghai Coll TCM New Drug Discovery, Engn Res Ctr, Shanghai 201203, Peoples R China; 4.Univ Chinese Acad Sci, Chinese Acad Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai Inst Nutr & Hlth,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Qiu, Yan,Sun, Yingmin,Yang, Yuanyuan,et al. Screening of FDA-approved drugs identifies sutent as a modulator of UCP1 expression in brown adipose tissue[J]. EBIOMEDICINE,2018,37(-):344-355. |
| APA | Qiu, Yan.,Sun, Yingmin.,Yang, Yuanyuan.,Liu, Xiaojian.,Wei, Yuda.,...&,.(2018).Screening of FDA-approved drugs identifies sutent as a modulator of UCP1 expression in brown adipose tissue.EBIOMEDICINE,37(-),344-355. |
| MLA | Qiu, Yan,et al."Screening of FDA-approved drugs identifies sutent as a modulator of UCP1 expression in brown adipose tissue".EBIOMEDICINE 37.-(2018):344-355. |
入库方式： OAI收割
来源：上海营养与健康研究所
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