SIM1 and obesity due to melanocortin 4 receptor deficiency: In view of the above data, the authors suggested a model arguing that Sim1 heterozygous phenotype of obesity and hyperphagia occur due to the Sim1 regulatory effect on OXT which is also severely depleted in Sim1 heterozygotes and melanocortin recptor-4 (Mc4r), both of which are known to function in appetite regulation (Kublaoui et al., 2006, 2008; Tolson et al., 2010).