In early obesity, adiponectin falls, particularly in inflamed EAT, and this reduction associates with reduced vasodilator tone and increased pro-oxidant cytokine action on endothelium and myocytes—an early lesion that couples early metabolic dysfunction to diastolic dysfunction and impaired exercise tolerance [7,22,23,32]. Here, ADIPOQ is linked to obesity due to melanocortin 4 receptor deficiency.