Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1
文献类型：期刊论文
| 作者 | Peng, Shiming; Xiao, Wen; Ju, Dapeng; Sun, Baofa; Hou, Nannan; Liu, Qianlan; Wang, Yanli; Zhao, Haijiao; Gao, Chunchun; Zhang, Song |
| 刊名 | SCIENCE TRANSLATIONAL MEDICINE
 |
| 出版日期 | 2019-04-17 |
| 卷号 | 11期号:488页码:- |
| ISSN号 | 1946-6234 |
| 英文摘要 | Recent studies have established the involvement of the fat mass and obesity-associated gene (FTO) in metabolic disorders such as obesity and diabetes. However, the precise molecular mechanism by which FTO regulates metabolism remains unknown. Here, we used a structure-based virtual screening of U.S. Food and Drug Administration-approved drugs to identify entacapone as a potential FTO inhibitor. Using structural and biochemical studies, we showed that entacapone directly bound to FTO and inhibited FTO activity in vitro. Furthermore, entacapone administration reduced body weight and lowered fasting blood glucose concentrations in diet-induced obese mice. We identified the transcription factor forkhead box protein O1 (FOXO1) mRNA as a direct substrate of FTO, and demonstrated that entacapone elicited its effects on gluconeogenesis in the liver and thermogenesis in adipose tissues in mice by acting on an FTO-FOXO1 regulatory axis. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/42959]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 作者单位 | 1.Chinese Acad Sci, Key Lab Genom & Precis Med, Beijing Inst Genom, 1 Beichen West Rd, Beijing 100101, Peoples R China 2.Fourth Mil Med Univ, State Key Lab Canc Biol, 127 West Changle Rd, Xian 710032, Shaanxi, Peoples R China 3.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Natl Inst Biol Sci, 7 Sci Pk Rd,Zhongguancun Life Sci Pk, Beijing 102206, Peoples R China |
| 推荐引用方式 GB/T 7714 | Peng, Shiming,Xiao, Wen,Ju, Dapeng,et al. Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1[J]. SCIENCE TRANSLATIONAL MEDICINE,2019,11(488):-. |
| APA | Peng, Shiming.,Xiao, Wen.,Ju, Dapeng.,Sun, Baofa.,Hou, Nannan.,...&Huang, Niu.(2019).Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1.SCIENCE TRANSLATIONAL MEDICINE,11(488),-. |
| MLA | Peng, Shiming,et al."Identification of entacapone as a chemical inhibitor of FTO mediating metabolic regulation through FOXO1".SCIENCE TRANSLATIONAL MEDICINE 11.488(2019):-. |
入库方式： OAI收割
来源：生态环境研究中心
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