Together, these observations not only clearly demonstrate that DNA methylation at the HOXA5 locus plays a role in the pathogenesis of obesity and its related disturbances, such as IR and T2D, but also suggest that the methylation status of HOXA5 may be useful in clinical practice as an epigenetic biomarker in the prediction and diagnosis of metabolic diseases (Table 1). This evidence concerns the gene HOXA5 and obesity due to melanocortin 4 receptor deficiency.