LEP and obesity due to melanocortin 4 receptor deficiency: Since leptin functions as a physiological and anorexic counteragent to ghrelin in the hypothalamus, blocking intraneuronal AG/GHS-R1α-signaling, some studies have suggested that the elevated plasma pools of leptin during obesity weaken the sensitivity toward AG (Hewson et al., 2002; Kohno et al., 2007; Briggs et al., 2014).