HIF1α-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages

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