Glycogen metabolism regulates macrophage-mediated acute inflammatory responses

Jingwei Ma, Keke Wei, Junwei Liu, Ke Tang, Huafeng Zhang, Liyan Zhu, Jie Chen, Fei Li, Pingwei Xu, Jie Chen, Jincheng Liu, Haiqing Fang, Liang Tang, Dianheng Wang, Liping Zeng, Weiwei Sun, Jing Xie, Yuying Liu and Bo Huang ()
Additional contact information
Jingwei Ma: Huazhong University of Science & Technology
Keke Wei: Huazhong University of Science & Technology
Junwei Liu: Huazhong University of Science & Technology
Ke Tang: Huazhong University of Science & Technology
Huafeng Zhang: Huazhong University of Science & Technology
Liyan Zhu: Huazhong University of Science & Technology
Jie Chen: Huazhong University of Science & Technology
Fei Li: Huazhong University of Science & Technology
Pingwei Xu: Huazhong University of Science & Technology
Jie Chen: Huazhong University of Science & Technology
Jincheng Liu: Huazhong University of Science & Technology
Haiqing Fang: Huazhong University of Science & Technology
Liang Tang: Huazhong University of Science & Technology
Dianheng Wang: Huazhong University of Science & Technology
Liping Zeng: Huazhong University of Science & Technology
Weiwei Sun: Huazhong University of Science & Technology
Jing Xie: Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College
Yuying Liu: Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College
Bo Huang: Huazhong University of Science & Technology

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Our current understanding of how sugar metabolism affects inflammatory pathways in macrophages is incomplete. Here, we show that glycogen metabolism is an important event that controls macrophage-mediated inflammatory responses. IFN-γ/LPS treatment stimulates macrophages to synthesize glycogen, which is then channeled through glycogenolysis to generate G6P and further through the pentose phosphate pathway to yield abundant NADPH, ensuring high levels of reduced glutathione for inflammatory macrophage survival. Meanwhile, glycogen metabolism also increases UDPG levels and the receptor P2Y14 in macrophages. The UDPG/P2Y14 signaling pathway not only upregulates the expression of STAT1 via activating RARβ but also promotes STAT1 phosphorylation by downregulating phosphatase TC45. Blockade of this glycogen metabolic pathway disrupts acute inflammatory responses in multiple mouse models. Glycogen metabolism also regulates inflammatory responses in patients with sepsis. These findings show that glycogen metabolism in macrophages is an important regulator and indicate strategies that might be used to treat acute inflammatory diseases.

Date: 2020
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DOI: 10.1038/s41467-020-15636-8

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