RFP cKO mice showed overall similar metabolic phenotypes to global RFP KO mice, particularly in terms of resistance to diet-induced obesity; when challenged with HFD, RFP cKO mice exhibited significant resistance to weight gain and adipose tissue accumulation compared with their control littermates (Fig. 4a–d), despite no significant differences in food intake or BAT weight (Supplementary Fig. 4c, d). Here, TRIM27 is linked to obesity due to melanocortin 4 receptor deficiency.