While a major leap was achieved by us and others a decade ago by inferring a causal variant in the obesity-associated FTO locus, identifying IRX3 and IRX5 as the target genes and adipocyte precursor cells as the effector cell type12, the question still remained how these genes mechanistically mediate the effect of the association3. This evidence concerns the gene IRX3 and obesity due to melanocortin 4 receptor deficiency.