Understanding the Brain

Central melanocortin system

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Anatomy

This system is defined anatomically as a collection of central nervous system circuits which include:

- Neurons that express hypothalamic neuropeptide Y and agouti gene-related protein or pro-opiomelanocortin and that originate in the arcuate nucleus.

- Brainstem pro-opiomelanocortic neurons originating in the commissural nucleus of the solitary tract.

- Downstream targets of these pro-opiomelanocortic and agouiti related protein neurons expressing the Melanocortin-3 and Melanocortin-4 receptors

Mechanism of Action

This system is involved in body weight regulation through its role in appetite and energy expenditure via Leptin, Grhelin and Agouti Related Protein. It receives inputs from hormones, nutrients and afferent neural inputs, and is unique in its composition of fibers which express both agonists and antagonists of melanocortin receptors.

Due to the prominence of obesity as a health concern, much funding and research has been invested in this area with respect to the Central Melanocortin System. However, it is important to note that this system also elicits effects on cardiovascular and sexual function.

Therapeutic Implications

This system is a target for drugs which treat obesity, diabetes and cachexia. Stimulation of the Melanocortin-4 receptor causes a decrease in appetite and an increase in metabolism of fat and lean body mass, even in a relatively starved state. Conversely, damage to this receptor has been shown to result in morbid obesity.

References

♦ Cone (2005) Anatomy and Regulation of the Central Melanocortin System Nature Neuroscience 7: 1048-54

♦ Daniel L. Marks, Nicholas Ling and Roger D. Cone (2001) Role of the Central Melanocortin System in Cachexia Cancer Research 61, 1432- 1438

♦ Joyce J. Hwa, Lorraine Ghibaudi, Jun Gao, and Eric M. Parker (2001) Central melanocortin system modulates energy intake and expenditure of obese and lean Zucker rats AJP-Regulatory, Integrative and Comparative Physiology Vol. 281, Issue 2, R444-R451