Importantly, Tfe3 KO mice showed down‐regulation of genes involved in thermogenesis, including Ucp1 and Ucp3, and oxidative genes such as Pparα in the BAT (Appendix Fig S3A and B), which account, at least partially, for their reduced energy expenditure and diet‐induced obesity. This evidence concerns the gene TFE3 and obesity due to melanocortin 4 receptor deficiency.