Dnmt1/3a ablation markedly inhibited weight gain (Fig. 6A), improved glucose tolerance (Fig. 6B,C) and insulin resistance (Fig. 6D,E), and decreased the enlarged white fat mass and adipocyte size in EP3F/FLysMCre mice (Fig. 6F–K), thereby reducing the elevated expression of fatty acid synthesis and adipogenic genes in the adipose tissues of EP3F/FLysMCre mice (Fig. 6L–P). Here, DNMT1 is linked to Insulin resistance.