Melanocortin Signaling Connecting Systemic Metabolism With Mood Disorders

Obesity and mood disorders are often overlapping pathologies that are prevalent public health concerns. Many studies have indicated a positive correlation between depression and obesity, although weight loss and decreased appetite are also recognized as features of depression. Accordingly, DSM-5 defines two subtypes of depression associated with changes in feeding: melancholic depression, characterized by anhedonia and associated with decreased feeding and appetite; and atypical depression, characterized by fatigue, sleepiness, hyperphagia, and weight gain. The central nervous system plays a key role in the regulation of feeding and mood, thus suggesting that overlapping neuronal circuits may be involved in their modulation. However, these circuits have yet to be completely characterized. The central melanocortin system, a circuitry characterized by the expression of specific peptides (pro-opiomelanocortins, agouti-related protein, and neuropeptide Y) and their melanocortin receptors, has been shown to be a key player in the regulation of feeding. In addition, the melanocortin system has also been shown to affect anxiety and depressive-like behavior, thus suggesting a possible role of the melanocortin system as a biological substrate linking feeding and depression. However, more studies are needed to fully understand this complex system and its role in regulating metabolic and mood disorders. In this review, we will discuss the current literature on the role of the melanocortin system in human and animal models in feeding and mood regulation, providing evidence of the biological interplay between anxiety, major depressive disorders, appetite, and body weight regulation.