In obesity, adipocyte hypertrophy results in decreased oxygen diffusion, leading to localized tissue AT hypoxia, as evidenced by upregulation of the hypoxia master regulator, hypoxia induced factor (HIF-1α), which stimulates MCP-1 and subsequent macrophage chemotaxis [143,186,187]. This evidence concerns the gene CCL2 and obesity due to melanocortin 4 receptor deficiency.