Obesity triggers hypoxia in adipose tissue and the small intestine, which stabilizes and activates hypoxia-inducible factor-1α (HIF-1α), a transcription factor implicated in hypoxia and hepatic lipid accumulation, resulting in adverse metabolic effects, including insulin resistance and NAFLD [1,3,4]. The gene discussed is HIF1A; the disease is obesity due to melanocortin 4 receptor deficiency.