Document Detail


Central lactate metabolism suppresses food intake via the hypothalamic AMP kinase/malonyl-CoA signaling pathway.
MedLine Citation:
PMID:  19523445     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous studies showed that centrally administered glucose and fructose exert different effects on food intake--glucose decreasing and fructose increasing food intake. Because of the uncertainty of whether fructose can cross the blood-brain-barrier, the question is raised; can dietary fructose directly enter the CNS? Evidence is presented that fructose administered by intraperitoneal (ip) injection to mice is rapidly (<10 min) converted to lactate in the hypothalamus. Thus, fructose can cross the blood-brain-barrier to enter the CNS/hypothalamus for conversion to lactate without prior (slower) conversion to glucose in the liver. Fructose-derived hypothalamic lactate is not, however, responsible for the orexigenic effect of fructose. Ip lactate administered at a level equivalent to that of fructose generates a higher level of hypothalamic lactate, which rapidly triggers dephosphorylation/inactivation of AMP-kinase. Thereby, ACC--a substrate of AMP-kinase that catalyzes malonyl-CoA formation--is dephosphorylated and activated. Consistent with these findings, ip or centrally (icv) administered lactate rapidly increases (<10 min) hypothalamic malonyl-CoA. Increasing hypothalamic malonyl-CoA suppresses the expression of the orexigenic and increases the expression of the anorexigenic neuropeptides, which decrease food intake. All downstream effects of hypothalamic lactate are blocked by icv administered oxamate, a potent inhibitor of lactate dehydrogenase, thus verifying the central action of lactate.
Authors:
Seung Hun Cha; M Daniel Lane
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Publication Detail:
Type:  Journal Article     Date:  2009-06-10
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  386     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-01     Completed Date:  2009-07-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  212-6     Citation Subset:  IM    
Affiliation:
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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MeSH Terms
Descriptor/Qualifier:
AMP-Activated Protein Kinases / metabolism*
Animals
Blood-Brain Barrier / metabolism
Eating / drug effects*
Fructose / administration & dosage,  metabolism
Hypothalamus / drug effects,  metabolism*
L-Lactate Dehydrogenase / antagonists & inhibitors,  metabolism
Lactic Acid / administration & dosage*,  metabolism*
Malonyl Coenzyme A / metabolism*
Mice
Neuropeptides / metabolism
Signal Transduction
Chemical
Reg. No./Substance:
0/Neuropeptides; 30237-26-4/Fructose; 50-21-5/Lactic Acid; 524-14-1/Malonyl Coenzyme A; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.7.11.1/AMP-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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