Document Detail

Activation of central orexin/hypocretin neurons by dietary amino acids.
MedLine Citation:
PMID:  22099463     Owner:  NLM     Status:  In-Data-Review    
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.
Mahesh M Karnani; John Apergis-Schoute; Antoine Adamantidis; Lise T Jensen; Luis de Lecea; Lars Fugger; Denis Burdakov
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neuron     Volume:  72     ISSN:  1097-4199     ISO Abbreviation:  Neuron     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8809320     Medline TA:  Neuron     Country:  United States    
Other Details:
Languages:  eng     Pagination:  616-29     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.
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