The above-mentioned could be concluded that caloric excess or diet-induced obesity triggered the activation of NF-κB pathway possibly via Tlr4 (of hepatocytes or Kupffer cells or both) resulting in the expression of proinflammatory cytokines such as TNF- α and IL-6, then amplification cascade of inflammation predisposed tissues and cells toward insulin resistance through the inhibition of insulin signaling. This evidence concerns the gene TLR4 and obesity due to melanocortin 4 receptor deficiency.