Genetic manipulation studies demonstrate EP3 deficiency leads to diet-induced obesity in mice through increase food uptake (Sanchez-Alavez et al, 2007), BAT whitening (Tao et al, 2022a) and WAT adipogenesis (Xu et al, 2016), indicating EP3 involvement of multiple organs/tissues (brain, BAT and WAT) in fat metabolism. This evidence concerns the gene PTGER3 and obesity due to melanocortin 4 receptor deficiency.