Claussnitzer et al. [65] identified the presence of an enhancer-acting element for IRX3 within a 10-kb gene range of the first intron of FTO in human cells, which contains a highly conserved variant of rs1421085 in which wild-type allele is T, whereas mutated allele with obesity risk is C. Under normal circumstance (wild-type: T), the cis-acting element, AATArITll, binds to the transcription factor ARID5B to inhibit the expression of IRX3, thereby promoting the expression of UCP1 in white fat tissues, increasing the basal metabolic rate, and inhibiting the occurrence of obesity [65]. Here, UCP1 is linked to obesity due to melanocortin 4 receptor deficiency.