Hypoxia induces adipocyte death and consequent macrophage recruitment (Cinti et al., 2005; Yin et al., 2009); these infiltrating cells, regulated primarily by HIF-1α, play a crucial role in initiating obesity-related disorders, including metabolic reprogramming, insulin resistance, and inflammation (Mazzatti et al., 2012). The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.