While one study showed homozygous ablation of Dnmt3a specifically in hypothalamic Sim1-positive neurons led to hyperphagia and obesity (Kohno et al., 2014), knockout of Dnmt3a in mature adipocytes protected mice from developing insulin resistance while on a high-fat-diet (You et al., 2017). Here, DNMT3A is linked to obesity due to melanocortin 4 receptor deficiency.