Thus, increased spontaneous burst-firing pattern (intra-burst frequency) in KLHL1-KO POMC neurons could enhance basal release of α-MSH from axon terminals, eventually leading to MC4R desensitization and constitutive, partially active satiety responses that would contribute to the obesity phenotype (Figure 8C, blue arrows; Gao et al., 2003; Shinyama et al., 2003; Mohammad et al., 2007; McDaniel et al., 2012; Granell et al., 2013). This evidence concerns the gene KLHL1 and obesity due to melanocortin 4 receptor deficiency.