INS and obesity due to melanocortin 4 receptor deficiency: In agreement with the literature, TNF-α is a central mediator of obesity-related metaflammation, since it promotes insulin resistance in the liver and skeletal muscle, impairs insulin signaling in adipocytes, increases lipolysis and free fatty acid flux to the liver, and contributes to endothelial activation and vascular dysfunction (Wu and Ballantyne, 2020).