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Melanocortin-4 receptor–regulated energy homeostasis

Nature Neuroscience volume 19, pages 206–219 (2016)Cite this article

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Abstract

The melanocortin system provides a conceptual blueprint for the central control of energetic state. Defined by four principal molecular components—two antagonistically acting ligands and two cognate receptors—this phylogenetically conserved system serves as a prototype for hierarchical energy balance regulation. Over the last decade the application of conditional genetic techniques has facilitated the neuroanatomical dissection of the melanocortinergic network and identified the specific neural substrates and circuits that underscore the regulation of feeding behavior, energy expenditure, glucose homeostasis and autonomic outflow. In this regard, the melanocortin-4 receptor is a critical coordinator of mammalian energy homeostasis and body weight. Drawing on recent advances in neuroscience and genetic technologies, we consider the structure and function of the melanocortin-4 receptor circuitry and its role in energy homeostasis.

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Figure 1: Genetically modified Mc4r alleles.
Figure 2: Melanocortins and the motivational basis of feeding.
Figure 3: Functional topography of Mc4r function.

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Acknowledgements

This work was supported by a University of Edinburgh Chancellor's Fellowship (A.S.G.) and US National Institutes of Health grants to B.B.L. (R01 DK096010, R01 DK089044, R01 DK071051, R01 DK075632, R37 DK053477, BNORC Transgenic Core P30 DK046200, BADERC Transgenic Core P30 DK057521) and to M.J.K. (Intramural Research Program, NIDDK; DK075087, DK075090).

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Authors and Affiliations

  1. Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Michael J Krashes

  2. National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA

    Michael J Krashes

  3. Division of Endocrinology, Department of Medicine, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Bradford B Lowell & Alastair S Garfield

  4. Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK

    Alastair S Garfield

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  1. Michael J Krashes
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Correspondence to Michael J Krashes or Alastair S Garfield.

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Krashes, M., Lowell, B. & Garfield, A. Melanocortin-4 receptor–regulated energy homeostasis. Nat Neurosci 19, 206–219 (2016). https://doi.org/10.1038/nn.4202

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