The signaling cascade of TNF-α is per si stimulated during obesity and hyperglycemia, causing an activation response of NF-κB that increases iNOS, which inhibits the substrate of the insulin receptor substrate 1 (IRS-1), and relates to the increase in OE, hindering the functioning of mitochondria and causing a reduction in β-oxidation [55,56,57,58]. Here, IRS1 is linked to obesity due to melanocortin 4 receptor deficiency.