| Activation of central orexin/hypocretin neurons by dietary amino acids. | |
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MedLine Citation:
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PMID: 22099463 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Hypothalamic orexin/hypocretin (orx/hcrt) neurons regulate energy balance, wakefulness, and reward; their loss produces narcolepsy and weight gain. Glucose can lower the activity of orx/hcrt cells, but whether other dietary macronutrients have similar effects is unclear. We show that orx/hcrt cells are stimulated by nutritionally relevant mixtures of amino acids (AAs), both in brain slice patch-clamp experiments, and in c-Fos expression assays following central or peripheral administration of AAs to mice in vivo. Physiological mixtures of AAs electrically excited orx/hcrt cells through a dual mechanism involving inhibition of K(ATP) channels and activation of system-A amino acid transporters. Nonessential AAs were more potent in activating orx/hcrt cells than essential AAs. Moreover, the presence of physiological concentrations of AAs suppressed the glucose responses of orx/hcrt cells. These results suggest a new mechanism of hypothalamic integration of macronutrient signals and imply that orx/hcrt cells sense macronutrient balance, rather than net energy value, in extracellular fluid. |
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Authors:
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Mahesh M Karnani; John Apergis-Schoute; Antoine Adamantidis; Lise T Jensen; Luis de Lecea; Lars Fugger; Denis Burdakov |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Neuron Volume: 72 ISSN: 1097-4199 ISO Abbreviation: Neuron Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8809320 Medline TA: Neuron Country: United States |
Other Details:
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Languages: eng Pagination: 616-29 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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