Although there are differences in the metabolic phenotypes depending on the models, Irx3- and Irx5-deficient mice are generally lean and display an anti-obesity phenotype with elevated energy expenditure due to adipose beiging (i.e., enhanced adipose thermogenesis) compared to wild-type controls (summarized in Table 1). Here, IRX5 is linked to obesity due to melanocortin 4 receptor deficiency.