Among these classical regulators of the insufficiency and/or dysfunction of circulating EPCs such as NO, VEGF, and GM-CSF [42, 43], and only NO production seems to be more likely to be responsible for the changes in circulating EPCs in many clinical or subclinical situations including obesity, smoke, prehypertension, and diabetes [11, 21, 24, 44]. The gene discussed is CSF2; the disease is obesity due to melanocortin 4 receptor deficiency.