Glycogen synthase

Inflammatory response

Cell biology

Glycogen

Biology

Glycolysis

Pentose phosphate pathway

GSK-3

Metabolism

Signal transduction

Biochemistry

Glycogenesis

Immunology

Glycogenolysis

In vitro

Macrophage

Inflammation

Medicine

Chemistry

GSK3B

Cellular metabolism

Carbohydrate metabolism

Nature Communications

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 P2Y 14 in macrophages. The UDPG/P2Y 14 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.

Glycogen metabolism regulates macrophage-mediated acute inflammatory responses