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Anatomy and regulation of the central melanocortin system

Abstract

The central melanocortin system is perhaps the best-characterized neuronal pathway involved in the regulation of energy homeostasis. This collection of circuits is unique in having the capability of sensing signals from a staggering array of hormones, nutrients and afferent neural inputs. It is likely to be involved in integrating long-term adipostatic signals from leptin and insulin, primarily received by the hypothalamus, with acute signals regulating hunger and satiety, primarily received by the brainstem. The system is also unique from a regulatory point of view in that it is composed of fibers expressing both agonists and antagonists of melanocortin receptors. Given that the central melanocortin system is an active target for development of drugs for the treatment of obesity, diabetes and cachexia, it is important to understand the system in its full complexity, including the likelihood that the system also regulates the cardiovascular and reproductive systems.

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Figure 1: Schematic of the central melanocortin system.
Figure 2: Schematic of the melanocortin system within the arcuate nucleus of the hypothalamus.
Figure 3: Distribution of POMC neurons within the nucleus tractus solitarius of the brainstem.

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Acknowledgements

The author would like to thank the many students, postdoctoral fellows and collaborators who participated in the work from his laboratory discussed in this review. The author would also like to thank L. Vaskalis for creating the illustrations. This work was funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

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Oregon Health and Science University (OHSU) and R.D.C. hold stock in Orexigen and Neurocrine Biosciences. These companies have licensed technology from OHSU of which Dr. Cone is an inventor. These technologies are used in some of the research reviewed in this article. This potential conflict was reviewed and a management plan approved by the OHSU Conflict of Interest in Research Committee.

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Cone, R. Anatomy and regulation of the central melanocortin system. Nat Neurosci 8, 571–578 (2005). https://doi.org/10.1038/nn1455

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