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论文题目: The metabolic ER stress sensor IRE1 alpha suppresses alternative activation of macrophages and impairs energy expenditure in obesity
英文论文题目: The metabolic ER stress sensor IRE1 alpha suppresses alternative activation of macrophages and impairs energy expenditure in obesity
第一作者: Shan, B; Wang, XX; Wu, Y; Xu, C; Xia, ZX; Dai, JL; Shao, ML; Zhao, F; He, SQ; Yang, L; Zhang, ML; Nan, FJ; Li, J; Liu, JM; Liu, JF; Jia, WP; Qiu, YF; Song, BL; Han, JDJ; Rui, LY; Duan, SZ; Liu, Y
英文第一作者: Shan, B; Wang, XX; Wu, Y; Xu, C; Xia, ZX; Dai, JL; Shao, ML; Zhao, F; He, SQ; Yang, L; Zhang, ML; Nan, FJ; Li, J; Liu, JM; Liu, JF; Jia, WP; Qiu, YF; Song, BL; Han, JDJ; Rui, LY; Duan, SZ; Liu, Y
联系作者: Duan, SZ (reprint author), Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China.
英文联系作者: Duan, SZ (reprint author), Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China.
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发表年度: 2017
卷: 18
期: 5
页码: 519-529
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.
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.
刊物名称: NATURE IMMUNOLOGY
英文刊物名称: NATURE IMMUNOLOGY
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学科: Immunology
英文学科: Immunology
影响因子: 21.506
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论文类别: Article
英文论文类别: Article
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