HIF1<i>α</i>-Induced Glycolysis Metabolism Is Essential to the Activation of Inflammatory Macrophages

Abstract

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