For example, obesity can elicit microgliosis and activation of microglial TGF-β-activated kinase 1 (Tak1), which further increases the secretion of IL-18 that directly inhibits the activity of endothelial nitric oxide synthase (eNOS) and hence eliminates NO production, leading to cerebrovascular dysfunction [111]. The gene discussed is NOS3; the disease is obesity due to melanocortin 4 receptor deficiency.