Intriguingly, the TF RREB1 whose gene locus has been linked to metabolic traits like T2D susceptibility, fasting glucose levels, and body fat distribution [37–39] through genome-wide association studies (GWAS), was up-regulated during brown adipogenesis and also associated with a SE defined by H3K27ac enrichment (Fig 3F). This evidence concerns the gene RREB1 and type 2 diabetes mellitus.