Dynamic MTORC1-TFEB feedback signaling regulates hepatic autophagy, steatosis and liver injury in long-term nutrient oversupply
文献类型：期刊论文
| 作者 | Zhang, Hao2; Yan, Shengmin2; Khambu, Bilon2; Li, Yong2; Chen, Xiaoyun2; Yin, Xiao-Ming2,6; Ma, Fengguang1; Li, Yu1; Martina, Jose. A.6; Puertollano, Rosa6 |
| 刊名 | AUTOPHAGY
 |
| 出版日期 | 2018 |
| 卷号 | 14期号:10页码:1779-1795 |
| 关键词 | Autophagy high-fat diet lipophagy lysosome MTORC1 NAFLD TFEB |
| ISSN号 | 1554-8627 |
| DOI | 10.1080/15548627.2018.1490850 |
| 文献子类 | Article |
| 英文摘要 | Normal metabolism requires a controlled balance between anabolism and catabolism. It is not completely known how this balance can be retained when the level of nutrient supply changes in the long term. We found that in murine liver anabolism, as represented by the phosphorylation of RPS6KB (ribosomal protein S6 kinase), was soon elevated while catabolism, as represented by TFEB (transcription factor EB)-directed gene transcription and lysosomal activities, was downregulated after the administration of a high-fat diet (HFD). Surprisingly, neither the alteration in RPS6KB phosphorylation nor that in TFEB functions was static over the long course of HFD feeding. Instead, the 2 signals exhibited dynamic alterations in opposite directions, which could be explained by the dependence of MTORC1 (MTOR complex 1) activation on TFEB-supported lysosome function and the feedback suppression of TFEB by MTORC1. Disruption of the dynamics by enforced expression of TFEB in HFD-fed mice at the peaks of MTORC1 activation restored lysosome function. Consistently, interference of MTORC1 activation with rapamycin or with a constitutively activated RRAGA mutant at the peak or nadir of MTORC1 oscillation enhanced or reduced the lysosome function, respectively. These treatments also improved or exacerbated hepatic steatosis and liver injury, respectively. Finally, there was a significant inverse correlation between TFEB activation and steatosis severity in the livers of patients with non-alcohol fatty liver diseases, supporting the clinical relevance of TFEB-regulated events. Thus, maintaining catabolic function through feedback mechanisms during enhanced anabolism, which is caused by nutrient oversupply, is important for reducing liver pathology. |
| 学科主题 | Cell Biology |
| WOS关键词 | LIPID-METABOLISM ; RAG GTPASES ; LYSOSOMAL BIOGENESIS ; AMINO-ACIDS ; MTOR ; LOOP ; GENE ; TFEB ; ACTIVATION ; INTEGRATION |
| 语种 | 英语 |
| WOS记录号 | WOS:000444087300010 |
| 出版者 | TAYLOR & FRANCIS INC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/861]  |
| 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.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China; 2.Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA; 3.Fudan Inst Metab Dis, Shanghai, Peoples R China, 4.Fudan Univ, Shanghai Zhongshan Hosp, Dept Endocrinol & Metab, Shanghai, Peoples R China; 5.Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA; 6.NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA; |
| 推荐引用方式 GB/T 7714 | Zhang, Hao,Yan, Shengmin,Khambu, Bilon,et al. Dynamic MTORC1-TFEB feedback signaling regulates hepatic autophagy, steatosis and liver injury in long-term nutrient oversupply[J]. AUTOPHAGY,2018,14(10):1779-1795. |
| APA | Zhang, Hao.,Yan, Shengmin.,Khambu, Bilon.,Li, Yong.,Chen, Xiaoyun.,...&,.(2018).Dynamic MTORC1-TFEB feedback signaling regulates hepatic autophagy, steatosis and liver injury in long-term nutrient oversupply.AUTOPHAGY,14(10),1779-1795. |
| MLA | Zhang, Hao,et al."Dynamic MTORC1-TFEB feedback signaling regulates hepatic autophagy, steatosis and liver injury in long-term nutrient oversupply".AUTOPHAGY 14.10(2018):1779-1795. |
入库方式： OAI收割
来源：上海营养与健康研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。