LEP and obesity due to melanocortin 4 receptor deficiency: Within the ARC, leptin acts on NPY/AgRP and POMC neurons (down-regulates Npy/Agrp expression and up-regulates Pomc expression) to decrease food intake and body weight; a loss of leptin’s actions causes increased orexigenic NPY/AgRP and decreased anorexigenic αMSH signals, leading to hyperphagia and obesity (Cone, 2006; Morton et al., 2006; Gautron and Elmquist, 2011; Friedman, 2014).