TNF and obesity due to melanocortin 4 receptor deficiency: The chronic low-grade inflammation in obesity disrupts the endocrine and paracrine signaling of adipose tissue, leading to the dysregulation of adipokine secretion, excess of tumor necrosis factor-alpha (TNF-alpha) and 2.5-fold increased vascular expression of endothelin-1 (ET-1) which consequently leads to impaired nitric oxide (NO) bioavailability and enhanced production of reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase2 (NOX2) and uncoupling of endothelial nitric oxide synthase (eNOS).