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ShanghaiTech University Knowledge Management System
| Fibroblast Growth Factor 21 Improves Hepatic Insulin Sensitivity by Inhibiting Mammalian Target of Rapamycin Complex 1 in Mice | |
| 2016-08 | |
| 发表期刊 | HEPATOLOGY (IF:12.9[JCR-2023],15.5[5-Year]) |
| ISSN | 0270-9139 |
| 卷号 | 64期号:2页码:425-438 |
| 发表状态 | 已发表 |
| DOI | 10.1002/hep.28523 |
| 摘要 | Among the 22 fibroblast growth factors (FGFs), FGF21 has now emerged as a key metabolic regulator. However, the mechanism whereby FGF21 mediates its metabolic actions per se remains largely unknown. Here, we show that FGF21 represses mammalian target of rapamycin complex 1 (mTORC1) and improves insulin sensitivity and glycogen storage in a hepatocyte-autonomous manner. Administration of FGF21 in mice inhibits mTORC1 in the liver, whereas FGF21-deficient mice display pronounced insulin-stimulated mTORC1 activation and exacerbated hepatic insulin resistance (IR). FGF21 inhibits insulin- or nutrient-stimulated activation of mTORC1 to enhance phosphorylation of Akt in HepG2 cells at both normal and IR condition. TSC1 deficiency abrogates FGF21-mediated inhibition of mTORC1 and augmentation of insulin signaling and glycogen synthesis. Strikingly, hepatic Klotho knockdown or hepatic hyperactivation of mTORC1/ribosomal protein S6 kinase 1 abrogates hepatic insulin-sensitizing and glycemic-control effects of FGF21 in diet-induced insulin-resistant mice. Moreover, FGF21 improves methionine- and choline-deficient diet-induced steatohepatitis. Conclusions: FGF21 acts as an inhibitor of mTORC1 to control hepatic insulin action and maintain glucose homeostasis, and mTORC1 inhibition by FGF21 has the therapeutic potential for treating IR and type 2 diabetes. |
| 收录类别 | SCI |
| 语种 | 英语 |
| 资助项目 | Research Grants Council of Hong Kong[C7055-14G] ; Research Grants Council of Hong Kong[HKU783413] |
| WOS研究方向 | Gastroenterology & Hepatology |
| WOS类目 | Gastroenterology & Hepatology |
| WOS记录号 | WOS:000380034500015 |
| 出版者 | WILEY-BLACKWELL |
| WOS关键词 | FATTY LIVER-DISEASE ; LIPID-METABOLISM ; PPAR-ALPHA ; FGF21 ; OBESITY ; STEATOSIS ; FIBROBLAST-GROWTH-FACTOR-21 ; PGC-1-ALPHA ; HOMEOSTASIS ; ACTIVATION |
| 原始文献类型 | Article |
| 引用统计 | 正在获取...
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| 文献类型 | 期刊论文 |
| 条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1772 |
| 专题 | 生命科学与技术学院 生命科学与技术学院_博士生 |
| 通讯作者 | Li, Yu |
| 作者单位 | 1.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 4.Shanghai Normal Univ, Coll Life & Environm Sci, Shanghai, Peoples R China 5.Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong, Hong Kong, Peoples R China 6.Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China 7.Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China 8.Univ Hong Kong, Dept Pharmacol & Pharm, Hong Kong, Hong Kong, Peoples R China 9.Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA |
| 推荐引用方式 GB/T 7714 | Gong, Qi,Hu, Zhimin,Zhang, Feifei,et al. Fibroblast Growth Factor 21 Improves Hepatic Insulin Sensitivity by Inhibiting Mammalian Target of Rapamycin Complex 1 in Mice[J]. HEPATOLOGY,2016,64(2):425-438. |
| APA | Gong, Qi.,Hu, Zhimin.,Zhang, Feifei.,Cui, Aoyuan.,Chen, Xin.,...&Li, Yu.(2016).Fibroblast Growth Factor 21 Improves Hepatic Insulin Sensitivity by Inhibiting Mammalian Target of Rapamycin Complex 1 in Mice.HEPATOLOGY,64(2),425-438. |
| MLA | Gong, Qi,et al."Fibroblast Growth Factor 21 Improves Hepatic Insulin Sensitivity by Inhibiting Mammalian Target of Rapamycin Complex 1 in Mice".HEPATOLOGY 64.2(2016):425-438. |
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