Fibroblast growth factor 21 improves hepatic insulin sensitivity by inhibiting mammalian target of rapamycin complex 1 in mice
文献类型：期刊论文
| 作者 | Gong, Qi1; Hu, Zhimin1; Zhang, Feifei1; Cui, Aoyuan1; Chen, Xin2,3; Jiang, Haoyang1; Gao, Jing1; Chen, Xuqing4; Han, Yamei1; Liang, Qingning5,6 |
| 刊名 | Hepatology
 |
| 出版日期 | 2016-08-01 |
| 卷号 | 64期号:2页码:425-438 |
| ISSN号 | 0270-9139 |
| DOI | 10.1002/hep.28523 |
| 通讯作者 | Li, yu(liyu@sibs.ac.cn) |
| 英文摘要 | 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. |
| WOS关键词 | FATTY LIVER-DISEASE ; LIPID-METABOLISM ; PPAR-ALPHA ; FGF21 ; OBESITY ; STEATOSIS ; FIBROBLAST-GROWTH-FACTOR-21 ; PGC-1-ALPHA ; HOMEOSTASIS ; ACTIVATION |
| WOS研究方向 | Gastroenterology & Hepatology |
| WOS类目 | Gastroenterology & Hepatology |
| 语种 | 英语 |
| WOS记录号 | WOS:000380034500015 |
| 出版者 | WILEY-BLACKWELL |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2374568 |
| 专题 | 中国科学院大学 |
| 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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来源：中国科学院大学
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