However, DNA demethylation of CpG islands in the Prdm16 promoter, likely mediated by TET proteins, is required for its expression [119, 120], by which demethylation of the Prdm16 promoter improves brown/beige adipogenic capacity and alleviates obesity in aged mice challenged with high-fat diet [121]. This evidence concerns the gene PRDM16 and obesity due to melanocortin 4 receptor deficiency.