Thus, CPs, by virtue of their hypothalamic location, have the potential to disrupt energy homeostasis at many levels, resulting in a complex clinical picture of HO syndrome characterized by severe obesity associated with leptin-resistance, fatigue, hyperphagia, impaired satiety, decreased sympathetic tone, and low energy expenditure [15,54–58]. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.