| Adaptation of myocardial substrate metabolism to a ketogenic nutrient environment. | |
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MedLine Citation:
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PMID: 20529848 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Heart muscle is metabolically versatile, converting energy stored in fatty acids, glucose, lactate, amino acids, and ketone bodies. Here, we use mouse models in ketotic nutritional states (24 h of fasting and a very low carbohydrate ketogenic diet) to demonstrate that heart muscle engages a metabolic response that limits ketone body utilization. Pathway reconstruction from microarray data sets, gene expression analysis, protein immunoblotting, and immunohistochemical analysis of myocardial tissue from nutritionally modified mouse models reveal that ketotic states promote transcriptional suppression of the key ketolytic enzyme, succinyl-CoA:3-oxoacid CoA transferase (SCOT; encoded by Oxct1), as well as peroxisome proliferator-activated receptor alpha-dependent induction of the key ketogenic enzyme HMGCS2. Consistent with reduction of SCOT, NMR profiling demonstrates that maintenance on a ketogenic diet causes a 25% reduction of myocardial (13)C enrichment of glutamate when (13)C-labeled ketone bodies are delivered in vivo or ex vivo, indicating reduced procession of ketones through oxidative metabolism. Accordingly, unmetabolized substrate concentrations are higher within the hearts of ketogenic diet-fed mice challenged with ketones compared with those of chow-fed controls. Furthermore, reduced ketone body oxidation correlates with failure of ketone bodies to inhibit fatty acid oxidation. These results indicate that ketotic nutrient environments engage mechanisms that curtail ketolytic capacity, controlling the utilization of ketone bodies in ketotic states. |
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Authors:
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Anna E Wentz; D André d'Avignon; Mary L Weber; David G Cotter; Jason M Doherty; Robnet Kerns; Rakesh Nagarajan; Naveen Reddy; Nandakumar Sambandam; Peter A Crawford |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-06-07 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-02 Completed Date: 2010-09-20 Revised Date: 2011-08-25 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 24447-56 Citation Subset: IM |
Affiliation:
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Department of Medicine, Washington University, St Louis, Missouri 63108, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE14929; GSE21368 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carbon Isotopes / chemistry Coenzyme A-Transferases / metabolism Immunohistochemistry / methods Ketone Bodies / chemistry Ketones / chemistry Male Mice Mice, Inbred C57BL Mice, Transgenic Models, Biological Myocardium / metabolism* Myocytes, Cardiac / cytology Peroxisome Proliferator-Activated Receptors / metabolism Rats |
| Grant Support | |
ID/Acronym/Agency:
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DK020579/DK/NIDDK NIH HHS; DK073282/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carbon Isotopes; 0/Ketone Bodies; 0/Ketones; 0/Peroxisome Proliferator-Activated Receptors; EC 2.8.3.-/Coenzyme A-Transferases; EC 2.8.3.5/3-ketoacid CoA-transferase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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