The obesity-increasing effect of FTO rs1421085 has been shown to disrupt ARID5B-mediated repression of IRX3 and IRX5 expression in pre-adipocytes that in turn leads to the excessive accumulation of triglycerides, increased adipocytes size, reduced mitochondrial oxidative capacity, and reduced white adipocytes browning, resulting in reduced mitochondrial thermogenesis43. The gene discussed is IRX5; the disease is obesity due to melanocortin 4 receptor deficiency.