FTO and obesity due to melanocortin 4 receptor deficiency: previously demonstrated that obesity-associated FTO variants were positively associated with IRX3 expression in the brain (12), and observed a 25%–30% decrease in body weight in Irx3 global knockout mice fed a normocaloric diet (NCD) compared with wild-type controls, which was attributable to a significant increase in brown/beige adipocyte function.