Previous studies had documented that miR-138-5p could inhibit the promoter of the epigenetic regulator EZH2 in cancers, nervous system diseases, and obesity [26–28], and we found that miR-138-5p could interact with the 3′UTR of EZH2 and inhibit its expression, thereby suppressing M1 macrophage differentiation but promoting M2 polarization. This evidence concerns the gene EZH2 and obesity due to melanocortin 4 receptor deficiency.