Besides an increase in insulin resistance andinflammation in obesity, factors including reduced nitric oxide levels, increasedvasoconstrictor molecule levels, such as endothelin 1, angiotensin 2, andarachidonic acid, and decreased microvascular density, leading to tissue hypoxia andische­mia, have been implicated in microvascular changes to include narrowedarterioles and expanded venular diameter(16). This evidence concerns the gene EDN1 and obesity due to melanocortin 4 receptor deficiency.