Insulin resistance induced by hyperglycemia and obesity also converges with inflammation and immune modulation in the insulin receptor substrate 1 (IRS-1)/mitogen-activated protein kinase (MAPK)/Akt/phosphatidylinositol-3 kinase (PI3K) and NF-κB/IL-1β/TNF-α/interferon-γ (IFN-γ) pathways [18,43]. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.