HIF-1 alpha, a hypoxia inducible transcription factor, in macrophage promotes onset of insulin resistance and diabetes

Chronic inflammation is a pathophysiology of insulin resistance in obesity. Adipose tissue macrophages play important roles in this inflammatory process. Adipose tissue becomes hypoxic as obesity progresses. We investigated the role of hypoxia-inducible factor (HIF)-1α, a key factor to hypoxic conditions, in myeloid cells using myeloid cell-specific Hif-1α knockout mice (HIF-1α KO).　High-fat-diet(HFD) fed HIF-1α KO mice showed improved glucose tolerance and improved insulin sensitivity compared to HFD fed control mice. Inflammatory change was reduced in WAT of HIF-1α KO mice. Angiogenesis was improved and hypoxia was less in WAT of HIF-1α KO mice than in WAT of control mice. In conclusion, HIF-1α in myeloid cells contributes to the development of insulin resistance with inducing inflammatory response and suppressing angiogenesis mediated by adipose tissue hypoxia.