Because IL-12 and TNF-α are co-stimulators for IFN-α, one of the essential cytokines for regulation of the inflammation and insulin resistance in obesity [91], the up-regulation of IL-12 in the absence of TNF-α could act in a compensatory manner to induce and maintain appropriate IFN-α levels. This evidence concerns the gene TNF and obesity due to melanocortin 4 receptor deficiency.