There is sustained, abnormal cytoplasmic-nuclear signalling involving membrane tyrosine kinase receptors (TKR), NF-κB activation and hypoxia-inducible factor-1α (HIF-1α) stabilization, as well as many epigenetic modifications in individuals with obesity [3,12,13,18]. The gene discussed is HIF1A; the disease is obesity due to melanocortin 4 receptor deficiency.