One study showed the regulatory role of IRX3 in the browning of white adipose tissue (WAT) and obesity development through hypothalamus-specific (Insulin2-cre) Irx3 knockout mouse models (Smemo et al., 2014), while the other indicated that the FTO obesity-linked loci functioned as a body weight regulator by controlling IRX3 expression in the peripheral adipose tissue and IRX3 modulated the browning progress of WAT, which was further supported by adipose-specific (Ap2-cre) Irx3 knockout mice (Claussnitzer et al., 2015). Here, IRX3 is linked to obesity due to melanocortin 4 receptor deficiency.