Pro-inflammatory polarization of T helper (Th) lymphocytes, with hyperactivated Interferon-γ (IFN-γ) and interleukin-17 (IL-17) producing Th subsets (Th1 and Th17) and/or impaired regulatory T cells (Tregs), could directly trigger the activation of the innate immunity, and subsequently lead to meta-inflammation and insulin resistance in obesity and T2D (8). The gene discussed is IL17A; the disease is obesity due to melanocortin 4 receptor deficiency.