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Insulin-Stimulated Cardiac Glucose Oxidation Is Increased in High-Fat Diet–Induced Obese Mice Lacking Malonyl CoA Decarboxylase

OBJECTIVE: Whereas an impaired ability to oxidize fatty acids is thought to contribute to intracellular lipid accumulation, insulin resistance, and cardiac dysfunction, high rates of fatty acid oxidation could also impair glucose metabolism and function. We therefore determined the effects of diet-i...

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Autores principales: Ussher, John R., Koves, Timothy R., Jaswal, Jagdip S., Zhang, Liyan, Ilkayeva, Olga, Dyck, Jason R.B., Muoio, Deborah M., Lopaschuk, Gary D.
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712785/
https://www.ncbi.nlm.nih.gov/pubmed/19478144
http://dx.doi.org/10.2337/db09-0011
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author Ussher, John R.
Koves, Timothy R.
Jaswal, Jagdip S.
Zhang, Liyan
Ilkayeva, Olga
Dyck, Jason R.B.
Muoio, Deborah M.
Lopaschuk, Gary D.
author_facet Ussher, John R.
Koves, Timothy R.
Jaswal, Jagdip S.
Zhang, Liyan
Ilkayeva, Olga
Dyck, Jason R.B.
Muoio, Deborah M.
Lopaschuk, Gary D.
author_sort Ussher, John R.
collection PubMed
description OBJECTIVE: Whereas an impaired ability to oxidize fatty acids is thought to contribute to intracellular lipid accumulation, insulin resistance, and cardiac dysfunction, high rates of fatty acid oxidation could also impair glucose metabolism and function. We therefore determined the effects of diet-induced obesity (DIO) in wild-type (WT) mice and mice deficient for malonyl CoA decarboxylase (MCD(−/−); an enzyme promoting mitochondrial fatty acid oxidation) on insulin-sensitive cardiac glucose oxidation. RESEARCH DESIGN AND METHODS: WT and MCD(−/−) mice were fed a low- or high-fat diet for 12 weeks, and intramyocardial lipid metabolite accumulation was assessed. A parallel feeding study was performed to assess myocardial function and energy metabolism (nanomoles per gram of dry weight per minute) in isolated working hearts (+/– insulin). RESULTS: DIO markedly reduced insulin-stimulated glucose oxidation compared with low fat–fed WT mice (167 ± 31 vs. 734 ± 125; P < 0.05). MCD(−/−) mice subjected to DIO displayed a more robust insulin-stimulated glucose oxidation (554 ± 82 vs. 167 ± 31; P < 0.05) and less incomplete fatty acid oxidation, evidenced by a decrease in long-chain acylcarnitines compared with WT counterparts. MCD(−/−) mice had long-chain acyl CoAs similar to those of WT mice subjected to DIO but had increased triacylglycerol levels (10.92 ± 3.72 vs. 3.29 ± 0.62 μmol/g wet wt; P < 0.05). CONCLUSIONS: DIO does not impair cardiac fatty acid oxidation or function, and there exists disassociation between myocardial lipid accumulation and insulin sensitivity. Our results suggest that MCD deficiency is not detrimental to the heart in obesity.
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spelling pubmed-27127852010-08-01 Insulin-Stimulated Cardiac Glucose Oxidation Is Increased in High-Fat Diet–Induced Obese Mice Lacking Malonyl CoA Decarboxylase Ussher, John R. Koves, Timothy R. Jaswal, Jagdip S. Zhang, Liyan Ilkayeva, Olga Dyck, Jason R.B. Muoio, Deborah M. Lopaschuk, Gary D. Diabetes Original Article OBJECTIVE: Whereas an impaired ability to oxidize fatty acids is thought to contribute to intracellular lipid accumulation, insulin resistance, and cardiac dysfunction, high rates of fatty acid oxidation could also impair glucose metabolism and function. We therefore determined the effects of diet-induced obesity (DIO) in wild-type (WT) mice and mice deficient for malonyl CoA decarboxylase (MCD(−/−); an enzyme promoting mitochondrial fatty acid oxidation) on insulin-sensitive cardiac glucose oxidation. RESEARCH DESIGN AND METHODS: WT and MCD(−/−) mice were fed a low- or high-fat diet for 12 weeks, and intramyocardial lipid metabolite accumulation was assessed. A parallel feeding study was performed to assess myocardial function and energy metabolism (nanomoles per gram of dry weight per minute) in isolated working hearts (+/– insulin). RESULTS: DIO markedly reduced insulin-stimulated glucose oxidation compared with low fat–fed WT mice (167 ± 31 vs. 734 ± 125; P < 0.05). MCD(−/−) mice subjected to DIO displayed a more robust insulin-stimulated glucose oxidation (554 ± 82 vs. 167 ± 31; P < 0.05) and less incomplete fatty acid oxidation, evidenced by a decrease in long-chain acylcarnitines compared with WT counterparts. MCD(−/−) mice had long-chain acyl CoAs similar to those of WT mice subjected to DIO but had increased triacylglycerol levels (10.92 ± 3.72 vs. 3.29 ± 0.62 μmol/g wet wt; P < 0.05). CONCLUSIONS: DIO does not impair cardiac fatty acid oxidation or function, and there exists disassociation between myocardial lipid accumulation and insulin sensitivity. Our results suggest that MCD deficiency is not detrimental to the heart in obesity. American Diabetes Association 2009-08 2009-05-28 /pmc/articles/PMC2712785/ /pubmed/19478144 http://dx.doi.org/10.2337/db09-0011 Text en © 2009 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Article
Ussher, John R.
Koves, Timothy R.
Jaswal, Jagdip S.
Zhang, Liyan
Ilkayeva, Olga
Dyck, Jason R.B.
Muoio, Deborah M.
Lopaschuk, Gary D.
Insulin-Stimulated Cardiac Glucose Oxidation Is Increased in High-Fat Diet–Induced Obese Mice Lacking Malonyl CoA Decarboxylase
title Insulin-Stimulated Cardiac Glucose Oxidation Is Increased in High-Fat Diet–Induced Obese Mice Lacking Malonyl CoA Decarboxylase
title_full Insulin-Stimulated Cardiac Glucose Oxidation Is Increased in High-Fat Diet–Induced Obese Mice Lacking Malonyl CoA Decarboxylase
title_fullStr Insulin-Stimulated Cardiac Glucose Oxidation Is Increased in High-Fat Diet–Induced Obese Mice Lacking Malonyl CoA Decarboxylase
title_full_unstemmed Insulin-Stimulated Cardiac Glucose Oxidation Is Increased in High-Fat Diet–Induced Obese Mice Lacking Malonyl CoA Decarboxylase
title_short Insulin-Stimulated Cardiac Glucose Oxidation Is Increased in High-Fat Diet–Induced Obese Mice Lacking Malonyl CoA Decarboxylase
title_sort insulin-stimulated cardiac glucose oxidation is increased in high-fat diet–induced obese mice lacking malonyl coa decarboxylase
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712785/
https://www.ncbi.nlm.nih.gov/pubmed/19478144
http://dx.doi.org/10.2337/db09-0011
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