Indeed, hypoxia has been observed in adipose tissue of obese humans and rodents, which is considered to be a potential factor for inducing adipose inflammation.113,114 In primary and cultured adipocytes, hypoxia has been shown to induce expression of many proinflammatory genes such as TNF-α, IL-1, IL-6, MCP-1, macrophage migration inhibitory factor (MIF), and matrix metalloproteinases 2 (MMP2) and 9 (MMP9).112,114 Hypoxia is also a potential contributor to the increase of adipocyte death in obesity, which is linked to the influx of proinflammatory M1 macrophages.115. The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.