INS and obesity due to melanocortin 4 receptor deficiency: On the other hand, the combination of a high-caloric food intake and a sedentary lifestyle has been suggested as the most important etiological cause of obesity (Seaman, 2013), and this environment favors dysregulation of energy homeostasis, since diet-induced hypothalamic inflammation has been indicated as the earliest factor leading to insulin and leptin resistance in the hypothalamus (Dragano et al., 2017).