In MMTV-Wnt-1 transgenic mice with diet-induced obesity (DIO), it was found by using RNA-sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) that leptin acts as a master regulator of the EMT gene signature by up-regulation of AKT3, PIK3R1, TWIST1, TWIST2, WNT11, and WNT9B. These mice also showed an up-regulation of the AKT3, WNT11, FRAT1, and WNT9B genes from the Wnt/β-catenin signaling, which is also related to the EMT program. Here, TWIST1 is linked to obesity due to melanocortin 4 receptor deficiency.