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  • Glycogen metabolism regulates macrophage-mediated acute inflammatory responses.

Glycogen metabolism regulates macrophage-mediated acute inflammatory responses.

Nature communications (2020-04-15)
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, Bo Huang
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-β-Actin antibody, Mouse monoclonal, clone AC-15, purified from hybridoma cell culture
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Glucose (GO) Assay Kit, sufficient for 20 assays
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Anti-Retinoic Acid Receptor β, C-Terminal antibody produced in rabbit, affinity isolated antibody
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Periodic Acid-Schiff (PAS) Staining System