LEP and obesity due to melanocortin 4 receptor deficiency: As gene hypomethylation is typically linked to increased gene activity (decreased gene silencing), the relationship between leptin gene hypomethylation and obesity may reflect the leptin resistance observed in obese populations as dysregulated exposure to a stimulus can result in a decreased sensitivity of receptors to that stimulus [13]. In other words, being obese may cause increased leptin release as the body attempts to correct the excessive energy intake by upregulating appetite suppression to control tendencies to overindulge.