TGFA and obesity due to melanocortin 4 receptor deficiency: Insulin resistance coupled with hyperinsulinemia and up-regulated insulin growth factor-1 are not only seen in diabetes but also has a tight association with hyperglycemia, obesity, and cancer development [328].In MetS patients, obesity-related inflammation induces the expression of a cluster of inflammatory cytokines including C-reactive protein (CRP), IL-6, TGF-α, and plasminogen activator inhibitor-1 (PAI-1) [329, 330], which further influence insulin signaling pathways and lead to insulin resistance.