LEP and obesity due to melanocortin 4 receptor deficiency: However, the inability of POMC-ObRb deficient models to recapitulate Ob/Ob or Db/Db levels of diet-induced obesity (DIO) indicates a role for leptin signalling in energy homeostasis outside of the hypothalamic ARC-PVN circuit (Figure 2) (Balthasar et al. 2004; Wall et al. 2008).