FTO and obesity due to melanocortin 4 receptor deficiency: 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.