Leptin acts as an energy status signal to reduce food intake and body weight during times of nutritional abundance, whereas mutation of leptin or LepRb results in severe hyperphagia, decreased energy expenditure, and early onset obesity in humans and rodents (Tartaglia et al., 1995; Chua et al., 1996; Montague et al., 1997; Farooqi et al., 1999; Kelesidis et al., 2010). Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.