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The metabolic ER stress sensor IRE1 alpha suppresses alternative activation of macrophages and impairs energy expenditure in obesity

文献类型：期刊论文

作者Shan, Bo9; Wang, Xiaoxia9; Wu, Ying9; Xu, Chi8; Xia, Zhixiong7; Dai, Jianli9; Shao, Mengle6; Zhao, Feng9; He, Shengqi5,9; Yang, Liu4
刊名NATURE IMMUNOLOGY
出版日期2017-05
卷号18期号:5页码:519-529
ISSN号1529-2908
DOI10.1038/ni.3709
文献子类Article
英文摘要Obesity is associated with metabolic inflammation and endoplasmic reticulum (ER) stress, both of which promote metabolic disease progression. Adipose tissue macrophages (ATMs) are key players orchestrating metabolic inflammation, and ER stress enhances macrophage activation. However, whether ER stress pathways underlie ATM regulation of energy homeostasis remains unclear. Here, we identified inositol-requiring enzyme 1 alpha (IRE1 alpha) as a critical switch governing M1-M2 macrophage polarization and energy balance. Myeloid-specific IRE1 alpha abrogation in Ern1(f/f); Lyz2-Cre mice largely reversed high-fat diet (HFD)-induced M1-M2 imbalance in white adipose tissue (WAT) and blocked HFD-induced obesity, insulin resistance, hyperlipidemia and hepatic steatosis. Brown adipose tissue (BAT) activity, WAT browning and energy expenditure were significantly higher in Ern1(f/f); Lyz2-Cre mice. Furthermore, IRE1 alpha ablation augmented M2 polarization of macrophages in a cell-autonomous manner. Thus, IRE1 alpha senses protein unfolding and metabolic and immunological states, and consequently guides ATM polarization. The macrophage IRE1 alpha pathway drives obesity and metabolic syndrome through impairing BAT activity and WAT browning.
WOS关键词UNFOLDED PROTEIN RESPONSE ; ENDOPLASMIC-RETICULUM ; ADIPOSE-TISSUE ; BEIGE FAT ; POLARIZATION ; DISEASE ; INSULIN ; CELL ; THERMOGENESIS ; INFLAMMATION
资助项目Ministry of Science and Technology[2016YFA0500100] ; Ministry of Science and Technology (973 Program)[2012CB524900] ; National Natural Science Foundation of China[81420108006] ; National Natural Science Foundation of China[31690102] ; National Natural Science Foundation of China[31230036] ; National Natural Science Foundation of China[31671181] ; National Natural Science Foundation of China[31371153] ; National Natural Science Foundation of China[91539107] ; National Natural Science Foundation of China[31671227] ; National Natural Science Foundation of China[91642113] ; European Foundation for the Study of Diabetes/Chinese Diabetes Society/Lilly Programme[00000000]
WOS研究方向Immunology
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000399378700009
源URL[http://119.78.100.183/handle/2S10ELR8/272689]  
专题国家新药筛选中心
药物安全性评价中心
通讯作者Duan, Sheng-Zhong; Liu, Yong
作者单位1.Univ Michigan, Med Sch, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA
2.Peking Univ, Beijing Key Lab Cardiometab Mol Med, Acad Adv Interdisciplinary Studies, Inst Mol Med,Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai, Peoples R China;
4.Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai Diabet Inst,Shanghai Key Lab Diabet Mell, Shanghai Clin Ctr Diabet,Dept Endocrinol & Metab, Shanghai, Peoples R China;
5.Wuhan Univ, Inst Adv Studies, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan, Peoples R China;
6.Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Touchstone Diabet Ctr, Dallas, TX 75390 USA;
7.Huazhong Univ Sci & Technol, Minist Educ, Key Lab Mol Biophys, Cellular Signaling Lab, Wuhan, Peoples R China;
8.Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Computat Biol, Chinese Acad Sci Max Planck Partner Inst Computat, Shanghai, Peoples R China;
9.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China;
推荐引用方式
GB/T 7714		 Shan, Bo,Wang, Xiaoxia,Wu, Ying,et al. The metabolic ER stress sensor IRE1 alpha suppresses alternative activation of macrophages and impairs energy expenditure in obesity[J]. NATURE IMMUNOLOGY,2017,18(5):519-529.
APA Shan, Bo.,Wang, Xiaoxia.,Wu, Ying.,Xu, Chi.,Xia, Zhixiong.,...&Liu, Yong.(2017).The metabolic ER stress sensor IRE1 alpha suppresses alternative activation of macrophages and impairs energy expenditure in obesity.NATURE IMMUNOLOGY,18(5),519-529.
MLA Shan, Bo,et al."The metabolic ER stress sensor IRE1 alpha suppresses alternative activation of macrophages and impairs energy expenditure in obesity".NATURE IMMUNOLOGY 18.5(2017):519-529.

入库方式： OAI收割

来源：上海药物研究所

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