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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, Mengle; Shan, Bo; Liu, Yang; Deng, Yiping; Yan, Cheng; Wu, Ying; Mao, Ting; Qiu, Yifu; Zhou, Yubo; Jiang, Shan |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2014 |
| 卷号 | 5期号:1页码:3528 |
| 通讯作者 | Liu, Y (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai 200031, Peoples R China. |
| 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. |
| 类目[WOS] | Multidisciplinary Sciences |
| 研究领域[WOS] | Science & Technology - Other Topics |
| 关键词[WOS] | UNFOLDED PROTEIN RESPONSE ; ENDOPLASMIC-RETICULUM STRESS ; PANCREATIC BETA-CELLS ; ER STRESS ; TRANSCRIPTION FACTOR ; MESSENGER-RNA ; PPAR-ALPHA ; TRANSMEMBRANE PROTEIN ; GLUCOSE-HOMEOSTASIS ; LIPID HOMEOSTASIS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000334302800001 |
| 公开日期 | 2015-12-24 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/276]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_糖脂代谢与调控研究组 |
| 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(1):3528. |
| 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(1),3528. |
| MLA | Shao, Mengle,et al."Hepatic IRE1 alpha regulates fasting-induced metabolic adaptive programs through the XBP1s-PPAR alpha axis signalling".NATURE COMMUNICATIONS 5.1(2014):3528. |
入库方式： OAI收割
来源：上海营养与健康研究所
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