Together, the present findings, generated from a mouse model of diet-induced obesity and adipose tissue from obese humans, suggest that inhibiting VAT lipolysis prevents the impairment of endothelial Kir2.1, further supporting the role of VAT-derived FAs in governing Kir2.1 dysfunction in obesity. This evidence concerns the gene KCNJ2 and obesity due to melanocortin 4 receptor deficiency.