HIF1 alpha-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages

Hypoxia-inducible factor (HIF) 1 alpha is a metabolic regulator that plays an important role in immunologic responses. Previous studies have demonstrated that HIF1 alpha participates in the M1 polarization of macrophages. To clarify the mechanism of HIF1 alpha-induced polarization of M1 macrophage, myeloid-specific HIF1 alpha overexpression (Lysm HIF1 alpha lsl) mice were employed and the bone marrow-derived and peritoneal macrophages were isolated. RT-PCR results revealed that HIF1 alpha overexpression macrophage had a hyperinflammatory state characterized by the upregulation of M1 markers. Cellular bioenergetics analysis showed lower cellular oxygen consumption rates in the Lysm HIF1 alpha lsl mice. Metabolomics studies showed that HIF1 alpha overexpression led to increased glycolysis and pentose phosphate pathway intermediates. Further results revealed that macrophage M1 polarization, induced by HIF1 alpha overexpression, was via upregulating the mRNA expression of the genes related to the glycolysis metabolism. Our results indicate that HIF1 alpha promoted macrophage glycolysis metabolism, which induced M1 polarization in mice.