Endothelial dysfunction, typically characterized by a reduced bioavailability of NO, has been observed previously in experimental models of vascular disease, including the diet-induced obesity mouse model (Weisbrod et al., 2013), pre-atherosclerotic apoE-/- mice (Fransen et al., 2008) and rodent models of hypertension (Küng and Lüscher, 1995) and is a common and well recognized early feature of vascular aging in humans (Kaess et al., 2012). The gene discussed is APOE; the disease is obesity due to melanocortin 4 receptor deficiency.