Obesity-induced adipose stress leads to the upregulation of ligands for natural cytotoxicity triggering receptor 1(NCR1) on adipocytes, which promotes the activation of NK cells to proliferate, and the release of IFN-γ induces macrophage polarization, which leads to glucose metabolism abnormality and insulin resistance, which suggests that NK cells can exacerbate the metabolic disorders through the cytokine release to exacerbate the symptoms of metabolic diseases [117]. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.