LEP and obesity due to melanocortin 4 receptor deficiency: The eCB/CB1R system is highly overactive during obesity (Engeli, 2008; Engeli et al., 2005; Matias et al., 2006; Monteleone et al., 2005), and both central and peripheral stimulations of this system have been suggested to contribute to the development of the metabolic syndrome, including leptin resistance (Engeli et al., 2005; Matias et al., 2008; Pagotto et al., 2005).