Hence, null mutations in the genes that encode for leptin or LepR impair the capacity of the hypothalamus to regulate energy homeostasis, leading to profound metabolic dysfunctions in humans and rodents, including severe obesity, hyperphagia, low-energy expenditure, hypoactivity, insulin resistance and infertility (Halaas et al., 1995; Montague et al., 1997; Farooqi et al., 2002; Licinio et al., 2004). Here, LEPR is linked to obesity due to melanocortin 4 receptor deficiency.