**5. Conclusions**

The pivotal role played by melanocortin system in controlling feeding behavior, appetite, energy balance and motivation for rewarding properties of food can explain why dysfunction of this system, in both human and rodent studies, results in a breakdown of normal regulatory processes and in more vulnerability to the loss of control in food intake, possibly leading to altered eating patterns, as summarized in Figure 2. Further research needs to highlight the mechanisms driving the hyperphagia in melanocortin-associated obesity, evidencing whether the exaggerated food consumption is accompanied by the loss of behavioral control, food seeking and/or binge eating episodes. Recent studies concerning MC3R and MC4R revealed that melanocortin signaling can exert functional effects in reward-related behaviors, due the hedonic properties of HPF, which is a potent natural reinforcer, and it has been postulated that in humans, low melanocortin activity could predispose individuals to pathological overeating, developing obesity and altered feeding behavior. Finally, the consistent relationship between the MC4R and stress response can be considered an additional factor linking melanocortin signaling to binge eating episodes, given the key role of stress in the etiology of this compulsive behavior. More preclinical studies are needed to investigate the biological mechanisms underlying dysfunctional eating patterns and clarify the possible connection between MCRs and binge eating behavior.

*Nutrients* **2020**, *12*, 3502

**Figure 2.** An overview of the altered eating patterns associated with the genetic variation of MC4R. ↓: decrease; ↑: increase; BMI: Body mass index; MC4R: Melanocortin-4 receptor.

**Author Contributions:** Conceptualization, E.M.D.B., L.B., M.V.M.D.B. and C.C.; writing—original draft preparation, E.M.D.B., L.B., M.V.M.D.B. and C.C.; writing—review and editing, E.M.D.B., L.B., D.T., S.K.T., M.V.M.D.B. and C.C.; visualization, E.M.D.B., L.B., D.T., S.K.T., M.V.M.D.B. and C.C.; supervision, M.V.M.D.B. and C.C.; funding acquisition, C.C. All authors have read and agreed to the published version of the manuscript.

**Funding:** The research was supported by grant PRIN2015KP7T2Y to C.C. of the Italian Ministry of Education, University and Research.

**Conflicts of Interest:** The authors declare no conflict of interest.
