Journal
NATURE NEUROSCIENCE
Volume 19, Issue 2, Pages 206-219Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.4202
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Funding
- University of Edinburgh
- US National Institutes of Health [R01 DK096010, R01 DK089044, R01 DK071051, R01 DK075632, R37 DK053477, P30 DK046200, P30 DK057521, DK075087, DK075090]
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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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