Through the engagement with membrane-bound TNF receptors (TNFRI and TNFRII), the post-receptor intracellular signaling of TNF-α involves c-Jun N-terminal kinase (JNK) and inhibitor of nuclear factor-κB kinase (IKK) to phosphorylate insulin receptor substrate-1 (IRS1) at the inhibitory residue serine-307 (in rodents, equivalent to serine-312 in humans), which is involved in insulin resistance [14,15]. This evidence concerns the gene IRS1 and Insulin resistance.