| Central lactate metabolism suppresses food intake via the hypothalamic AMP kinase/malonyl-CoA signaling pathway. | |
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MedLine Citation:
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PMID: 19523445 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Seung Hun Cha; M Daniel Lane |
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Publication Detail:
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Type: Journal Article Date: 2009-06-10 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 386 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-07-01 Completed Date: 2009-07-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 212-6 Citation Subset: IM |
Affiliation:
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Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases
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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:
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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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