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Melanocortin-4 receptor–regulated energy homeostasis | Nature Neuroscience
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Central melanocortinergic signaling via the melanocortin-4 receptor is both a culprit in and a target for obesity. The authors review our understanding of this evolutionarily conserved system in the regulation of mammalian energy homeostasis. 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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nature portfolio intramural research program permissions reprints privacy policy author information authors advertising agouti-related peptide-expressing neurons social media mc4r-deficient c57bl/6j mice agouti-related protein binding melanocortin-4 receptor-mediated inhibition nature 488 nature 411 nature 487 nature 503 nature 521 nature 520 nature mice lacking pro-opiomelanocortin agouti-related protein functions channelrhodopsin-2-assisted circuit mapping mitogen-activated protein kinase long-range callosal projections negative-valence teaching signal pro-opiomelanocortin deficiency responds melanocortin-4 receptor-regulated appetite g-protein-independent coupling divergent signal-transduction pathways γ2-melanocyte-stimulating hormones flip-flop memory circuit cholecystokinin-mediated suppression personal data central nervous system melanocortin-4 receptor-deficient mice mc4r-expressing glutamatergic neurons central melanocortin system pertussis toxin-sensitive signaling agouti-related protein severe early-onset obesity central melanocortin receptors alpha-melanocyte-stimulating hormone springerlink instant access data protection permissions central melanocortin pathways central melanocortin circuitry agouti-related peptide central receptors mediating taste aversion central melanocortinergic pathways
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headline:Melanocortin-4 receptorâregulated energy homeostasis
description:Central melanocortinergic signaling via the melanocortin-4 receptor is both a culprit in and a target for obesity. The authors review our understanding of this evolutionarily conserved system in the regulation of mammalian energy homeostasis. The melanocortin system provides a conceptual blueprint for the central control of energetic state. Defined by four principal molecular componentsâtwo antagonistically acting ligands and two cognate receptorsâthis 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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description:Central melanocortinergic signaling via the melanocortin-4 receptor is both a culprit in and a target for obesity. The authors review our understanding of this evolutionarily conserved system in the regulation of mammalian energy homeostasis. The melanocortin system provides a conceptual blueprint for the central control of energetic state. Defined by four principal molecular componentsâtwo antagonistically acting ligands and two cognate receptorsâthis 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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Neural circuits
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Animal Genetics and Genomics
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