While earlier studies in TNFα-receptor-deficient mice failed to support the concept that TNFα is a major contributor to obesity-associated insulin resistance, [77] increasing evidence supports a positive correlation between TNF-α-induced insulin resistance, NF-κB signaling, and pathogenesis of T2DM [48,78,79,80]. This evidence concerns the gene NFKB1 and obesity due to melanocortin 4 receptor deficiency.