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New ligands for melanocortin receptors

International Journal of Obesity volume 32, pages S19–S27 (2008)Cite this article

Abstract

Named originally for their effects on peripheral end organs, the melanocortin system controls a diverse set of physiological processes through a series of five G-protein-coupled receptors and several sets of small peptide ligands. The central melanocortin system plays an essential role in homeostatic regulation of body weight, in which two alternative ligands, α-melanocyte-stimulating hormone and agouti-related protein, stimulate and inhibit receptor signaling in several key brain regions that ultimately affect food intake and energy expenditure. Much of what we know about the relationship between central melanocortin signaling and body weight regulation stems from genetic studies. Comparative genomic studies indicate that melanocortin receptors used for controlling pigmentation and body weight regulation existed more than 500 million years ago in primitive vertebrates, but that fine-grained control of melanocortin receptors through neuropeptides and endogenous antagonists developed more recently. Recent studies based on dog coat-color genetics revealed a new class of melanocortin ligands, the β-defensins, which reveal the potential for cross talk between the melanocortin and the immune systems.

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Acknowledgements

Some of the work described was supported by grants from the National Institutes of Health to GSB and to GLM.

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Authors and Affiliations

  1. Department of Genetics, Stanford University, Stanford, CA, USA

    C B Kaelin, S I Candille, J Binkley & G S Barsh

  2. Department of Pediatrics, Stanford University, Stanford, CA, USA

    C B Kaelin, S I Candille, J Binkley & G S Barsh

  3. Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA, USA

    B Yu, P Jackson, D A Thompson, M A Nix & G L Millhauser

  4. Department of Pathology, Stanford University, Stanford, CA, USA

    J Binkley

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  1. C B Kaelin
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Pilgrim Jackson has equity ownership/stock options with Celgene. Gregory S Barsh has received consulting fees from Merck and grant support from NIH. The remaining authors have declared no financial interests.

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Kaelin, C., Candille, S., Yu, B. et al. New ligands for melanocortin receptors. Int J Obes 32 (Suppl 7), S19–S27 (2008). https://doi.org/10.1038/ijo.2008.234

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