The increased expression of UCP1 in WAT leads to energy expenditure and reduced lipid accumulation in adipocytes, resembling classic brown adipocyte functions.[3, 4] In our study, we found that the protein and mRNA levels of Ucp1 were increased in iWAT and from REGγ KO and REGγ AKO mice, as well as in primary adipocytes from iWAT of REGγ KO and REGγ AKO mice compared with controls (Figure 4d–h; Figure S4a–g, Supporting Information), indicating that REGγ might regulate the expression of UCP1 in browning of WAT to induce obesity. Here, UCP1 is linked to obesity due to melanocortin 4 receptor deficiency.