Additionally, all the previous effects, characteristic of severe obesity, are predominantly linked to MC4R mutations and defects in MC4R signaling in humans, compared to the alterations of MC3R, which frequently cause only moderate obesity or limited hyperphagia; to date, the role of MC3R remains an element that needs to be clarified [11,13,14,69,70,71,72]. This evidence concerns the gene MC4R and obesity due to melanocortin 4 receptor deficiency.