Hepatic IRE1 alpha regulates fasting-induced metabolic adaptive programs through the XBP1s-PPAR alpha axis signalling
文献类型：期刊论文
| 作者 | Shao, Mengle1,5; Shan, Bo1,5; Liu, Yang1,5; Deng, Yiping1,5; Yan, Cheng1,5; Wu, Ying1,5; Mao, Ting1,5; Qiu, Yifu1,5; Zhou, Yubo2 ; Jiang, Shan3
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| 刊名 | NATURE COMMUNICATIONS
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| 出版日期 | 2014-03 |
| 卷号 | 5 |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/ncomms4528 |
| 文献子类 | Article |
| 英文摘要 | Although the mammalian IRE1 alpha-XBP1 branch of the cellular unfolded protein response has been implicated in glucose and lipid metabolism, the exact metabolic role of IRE1 alpha signalling in vivo remains poorly understood. Here we show that hepatic IRE1 alpha functions as a nutrient sensor that regulates the metabolic adaptation to fasting. We find that prolonged deprivation of food or consumption of a ketogenic diet activates the IRE1 alpha-XBP1 pathway in mouse livers. Hepatocyte-specific abrogation of Ire1 alpha results in impairment of fatty acid beta-oxidation and ketogenesis in the liver under chronic fasting or ketogenic conditions, leading to hepatosteatosis; liver-specific restoration of XBP1s reverses the defects in IRE1 alpha null mice. XBP1s directly binds to and activates the promoter of PPAR alpha, the master regulator of starvation responses. Hence, our results demonstrate that hepatic IRE1 alpha promotes the adaptive shift of fuel utilization during starvation by stimulating mitochondrial beta-oxidation and ketogenesis through the XBP1s-PPAR alpha axis. |
| WOS关键词 | UNFOLDED PROTEIN RESPONSE ; ENDOPLASMIC-RETICULUM STRESS ; PANCREATIC BETA-CELLS ; ER STRESS ; TRANSCRIPTION FACTOR ; MESSENGER-RNA ; PPAR-ALPHA ; TRANSMEMBRANE PROTEIN ; GLUCOSE-HOMEOSTASIS ; LIPID HOMEOSTASIS |
| 资助项目 | Ministry of Science and Technology (973 Programs)[2012CB524900] ; Ministry of Science and Technology (973 Programs)[2011CB910900] ; National Natural Science Foundation of China[31230036] ; National Natural Science Foundation of China[81321062] ; National Natural Science Foundation of China[91213306] ; National Natural Science Foundation of China[30988002] ; Chinese Academy of Sciences (The Knowledge Innovation Program)[KSCX2-EW-R-09] ; Shanghai Postdoctoral Scientific Program[12R21417500] ; SA-SIBS Scholarship Program[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000334302800001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277164]  |
| 专题 | 国家新药筛选中心 药物安全性评价中心 |
| 通讯作者 | Liu, Yong |
| 作者单位 | 1.Univ Chinese Acad Sci, Shanghai 200031, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 3.Shanghai Jiao Tong Univ, Peoples Hosp 6, Shanghai Clin Ctr Diabet,Dept Endocrinol & Metab, Shanghai Diabet Inst,Shanghai Key Lab Diabet Mell, Shanghai 200233, Peoples R China; 4.Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA 5.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai 200031, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Shao, Mengle,Shan, Bo,Liu, Yang,et al. Hepatic IRE1 alpha regulates fasting-induced metabolic adaptive programs through the XBP1s-PPAR alpha axis signalling[J]. NATURE COMMUNICATIONS,2014,5. |
| APA | Shao, Mengle.,Shan, Bo.,Liu, Yang.,Deng, Yiping.,Yan, Cheng.,...&Liu, Yong.(2014).Hepatic IRE1 alpha regulates fasting-induced metabolic adaptive programs through the XBP1s-PPAR alpha axis signalling.NATURE COMMUNICATIONS,5. |
| MLA | Shao, Mengle,et al."Hepatic IRE1 alpha regulates fasting-induced metabolic adaptive programs through the XBP1s-PPAR alpha axis signalling".NATURE COMMUNICATIONS 5(2014). |
入库方式： OAI收割
来源：上海药物研究所
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