Therefore, the HO-mediated suppression of visceral and subcutaneous obesity when combined to other cytoprotective effects of the HO system such as the attenuation of NF-κB activity [41–44, 47, 83, 84, 203] may constitute a protective shield against insulin resistance, obesity, and other nutrition-overload related complication (Figure 2). This evidence concerns the gene HMOX1 and obesity due to melanocortin 4 receptor deficiency.