In turn, pro-inflammatory cytokines, such as TNF-α and IL-6, hyper-expressed by activated M1 macrophages, favor the increase in lipid deposition because hyperinsulinemia decreases the sensitivity of the insulin receptor at the CNS level, reducing the feeling of satiety, instead increasing the feeling of hyperphagia and, therefore, facilitating a positive energy balance which, in turn, favors the hypertrophy of the adipocytes, perpetuating the cycle of obesity–lipoinflammation–increased appetite [2,55]. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.