The Role of the Melanocortin System in Metabolic Disease: New Developments and Advances

Abstract

Obesity is increasing in prevalence across all sectors of society, and with it a constellation of associated ailments including hypertension, type 2 diabetes, and eating disorders. The melanocortin system is a critical neural system underlying the control of body weight and other functions. Deficits in the melanocortin system may promote or exacerbate the comorbidities of obesity. This system has therefore generated great interest as a potential target for treatment of obesity. However, drugs targeting melanocortin receptors are plagued by problematic side effects, including undesirable increases in sympathetic nervous system activity, heart rate, and blood pressure. Circumnavigating this roadblock will require a clearer picture of the precise neural circuits that mediate the functions of melanocortins. Recent, novel experimental approaches have significantly advanced our understanding of these pathways. We here review the latest advances in our understanding of the role of melanocortins in food intake, reward pathways, blood pressure, glucose control, and energy expenditure. The evidence suggests that downstream melanocortin-responsive circuits responsible for different physiological actions do diverge. Ultimately, a more complete understanding of melanocortin pathways and their myriad roles should allow treatments tailored to the mix of metabolic disorders in the individual patient.

Hypothalamic C2-domain protein involved in MC4R trafficking and control of energy balance

“…Previously, C2CD5 has been shown to be involved in GLUT4 trafficking in adipocytes [28], and, in insulin sensitivity and browning of adipose tissue [36]. So far, the expression and function of C2CD5 in the brain has not been reported.…”

“…AP2, clathrin heavy/light chains, dynamin1, 3) and components of plasma membrane. Based on these complementary approaches, we propose that C2CD5 is a novel hypothalamic protein responding to fat challenge, and is involved in trafficking in line with its role in adipose tissue [28].…”

“…Here, we identify a calcium-and lipid-binding C2 domain protein, C2CD5 [28] that contribute to regulation of MC4R endocytosis. C2CD5 is highly expressed in the hypothalamus and its level decreases in obesity and in presence of saturated fatty acids.…”

Hypothalamic C2-domain protein involved in MC4R trafficking and control of energy balance

“…The ability of melanocortin to suppress feeding and increase energy expenditure has made melanocortin receptors (MCR) the focus of many anti-obesity treatments. Melanocortin system controls many aspects of metabolism that can contribute to obesity and associated comorbidities [13]. Studies on spontaneous as well as genetically introduced variations in genes of the melanocortin system demonstrate the importance of this system in obesity and its associated metabolic syndrome, and suggest a dysfunction of the melanocortin system [13,14].…”

Influence of Semax on the Intensity of Redox Reactions in Immunocompetent Organs in the Conditions of "Social" Stress

“…A promising approach to the correction of impaired protective functions of the body due to stressful effects is the study and subsequent implementation of peptide drugs in practice [1]. As a promising means of correcting stress-induced immunity disorders, the drug Semax, which is a synthetic heptapeptide -an analogue of ACTH 4-10 (Met-Glu-His-Phe-Pro-Gly-Pro), is devoid of hormonal activity [3,8]. Despite the fact that Semax has been used in clinical practice for more than 20 years, the full range of pharmacological effects of this peptide has not yet been determined.…”