Identification of a rhodanine derivative BML-260 as a potent stimulator of UCP1 expression
文献类型：期刊论文
| 作者 | Feng, Zhuanghui1; Wei, Yuda1; Zhang, Yongxian1; Qiu, Yan1; Liu, Xiaojian1; Liang, Ningning1; Yin, Huiyong1; Ding, Qiurong1; Su, Li2; Ding, Qiurong3 |
| 刊名 | THERANOSTICS
 |
| 出版日期 | 2019 |
| 卷号 | 9期号:12页码:3501-3514 |
| ISSN号 | 1838-7640 |
| 关键词 | BML-260 Uncoupling protein 1 Adipocyte browning Mitochondrial activity |
| DOI | 10.7150/thno.31951 |
| 文献子类 | Article |
| 英文摘要 | Identification of proper agents to increase or activate UCP1(+) cells in adipose tissues remains a potent therapeutic strategy to combat obesity. Screening systems for UCPI activators have been previously established and allow for unbiased discovery of effective compound(s). Methods: A previously established Ucp1-2A-GFP reporter system was applied to a chemical library containing 33 phosphatase inhibitors. Compounds that can significantly activate UCP1 expression were further tested in vivo in mouse adipose tissues. Possible underlying mechanism was explored via RNA profiling, CMAP analysis, CRISPR targeting as well as inhibitor treatments. Results: We identified BML-260, a known potent inhibitor of the dual-specific phosphatase JSP-1, that significantly increased UCP1 expression in both brown and white adipocytes. BML-260 treatment also activated oxidative phosphorylation genes, increased mitochondrial activity as well as heat generation in vitro and in vivo. Mechanistic studies revealed that effect of BML-260 on adipocytes was partly through activated CREB, STAT3 and PPAR signaling pathways, and was unexpectedly JSP-1 independent. Conclusion: The rhodanine derivate BML-260 was previously identified to be a JSP-1 inhibitor, and thus was proposed to treat inflammatory and proliferative disorders associated with dysfunctional JNK signaling. This work provides evidences that BML-260 can also exert a JSP-1-independent effect in activating UCP1 and thermogenesis in adipocytes, and be potentially applied to treat obesity. |
| 学科主题 | Research & Experimental Medicine |
| WOS关键词 | BROWN ADIPOSE-TISSUE ; DRUG DISCOVERY ; MAP KINASE ; BEIGE FAT ; WHITE ; ADIPOCYTES ; OBESITY ; ACTIVATION ; THERMOGENESIS ; REVERSAL |
| 语种 | 英语 |
| 出版者 | IVYSPRING INT PUBL |
| WOS记录号 | WOS:000469953000008 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1006]  |
| 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, CAS Key Lab Nutr Metab & Food Safety, Shanghai Inst Nutr & Hlth, Univ Chinese Acad Sci,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China; 2.Shanghai Univ, Inst Translat Med, Shanghai, Peoples R China; 3.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Feng, Zhuanghui,Wei, Yuda,Zhang, Yongxian,et al. Identification of a rhodanine derivative BML-260 as a potent stimulator of UCP1 expression[J]. THERANOSTICS,2019,9(12):3501-3514. |
| APA | Feng, Zhuanghui.,Wei, Yuda.,Zhang, Yongxian.,Qiu, Yan.,Liu, Xiaojian.,...&,.(2019).Identification of a rhodanine derivative BML-260 as a potent stimulator of UCP1 expression.THERANOSTICS,9(12),3501-3514. |
| MLA | Feng, Zhuanghui,et al."Identification of a rhodanine derivative BML-260 as a potent stimulator of UCP1 expression".THERANOSTICS 9.12(2019):3501-3514. |
入库方式： OAI收割
来源：上海营养与健康研究所
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