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Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification

AIMS/HYPOTHESIS: Changes in cardiac substrate utilisation leading to altered energy metabolism may underlie the development of diabetic cardiomyopathy. We studied cardiomyocyte substrate uptake and utilisation and the role of the fatty acid translocase CD36 in relation to in vivo cardiac function in...

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Autores principales: Ouwens, D. M., Diamant, M., Fodor, M., Habets, D. D. J., Pelsers, M. M. A. L., El Hasnaoui, M., Dang, Z. C., van den Brom, C. E., Vlasblom, R., Rietdijk, A., Boer, C., Coort, S. L. M., Glatz, J. F. C., Luiken, J. J. F. P.
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2039861/
https://www.ncbi.nlm.nih.gov/pubmed/17639306
http://dx.doi.org/10.1007/s00125-007-0735-8
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author Ouwens, D. M.
Diamant, M.
Fodor, M.
Habets, D. D. J.
Pelsers, M. M. A. L.
El Hasnaoui, M.
Dang, Z. C.
van den Brom, C. E.
Vlasblom, R.
Rietdijk, A.
Boer, C.
Coort, S. L. M.
Glatz, J. F. C.
Luiken, J. J. F. P.
author_facet Ouwens, D. M.
Diamant, M.
Fodor, M.
Habets, D. D. J.
Pelsers, M. M. A. L.
El Hasnaoui, M.
Dang, Z. C.
van den Brom, C. E.
Vlasblom, R.
Rietdijk, A.
Boer, C.
Coort, S. L. M.
Glatz, J. F. C.
Luiken, J. J. F. P.
author_sort Ouwens, D. M.
collection PubMed
description AIMS/HYPOTHESIS: Changes in cardiac substrate utilisation leading to altered energy metabolism may underlie the development of diabetic cardiomyopathy. We studied cardiomyocyte substrate uptake and utilisation and the role of the fatty acid translocase CD36 in relation to in vivo cardiac function in rats fed a high-fat diet (HFD). METHODS: Rats were exposed to an HFD or a low-fat diet (LFD). In vivo cardiac function was monitored by echocardiography. Substrate uptake and utilisation were determined in isolated cardiomyocytes. RESULTS: Feeding an HFD for 8 weeks induced left ventricular dilation in the systolic phase and decreased fractional shortening and the ejection fraction. Insulin-stimulated glucose uptake and proline-rich Akt substrate 40 phosphorylation were 41% (p < 0.001) and 45% (p < 0.05) lower, respectively, in cardiomyocytes from rats on the HFD. However, long-chain fatty acid (LCFA) uptake was 1.4-fold increased (p < 0.001) and LCFA esterification into triacylglycerols and phospholipids was increased 1.4- and 1.5-fold, respectively (both p < 0.05), in cardiomyocytes from HFD compared with LFD hearts. In the presence of the CD36 inhibitor sulfo-N-succinimidyloleate, LCFA uptake and esterification were similar in LFD and HFD cardiomyocytes. In HFD hearts CD36 was relocated to the sarcolemma, and basal phosphorylation of a mediator of CD36-trafficking, i.e. protein kinase B (PKB/Akt), was increased. CONCLUSIONS/INTERPRETATION: Feeding rats an HFD induced cardiac contractile dysfunction, which was accompanied by the relocation of CD36 to the sarcolemma, and elevated basal levels of phosphorylated PKB/Akt. The permanent presence of CD36 at the sarcolemma resulted in enhanced rates of LCFA uptake and myocardial triacylglycerol accumulation, and may contribute to the development of insulin resistance and diabetic cardiomyopathy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-007-0735-8) contains supplementary material, which is available to authorised users.
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spelling pubmed-20398612007-10-29 Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification Ouwens, D. M. Diamant, M. Fodor, M. Habets, D. D. J. Pelsers, M. M. A. L. El Hasnaoui, M. Dang, Z. C. van den Brom, C. E. Vlasblom, R. Rietdijk, A. Boer, C. Coort, S. L. M. Glatz, J. F. C. Luiken, J. J. F. P. Diabetologia Article AIMS/HYPOTHESIS: Changes in cardiac substrate utilisation leading to altered energy metabolism may underlie the development of diabetic cardiomyopathy. We studied cardiomyocyte substrate uptake and utilisation and the role of the fatty acid translocase CD36 in relation to in vivo cardiac function in rats fed a high-fat diet (HFD). METHODS: Rats were exposed to an HFD or a low-fat diet (LFD). In vivo cardiac function was monitored by echocardiography. Substrate uptake and utilisation were determined in isolated cardiomyocytes. RESULTS: Feeding an HFD for 8 weeks induced left ventricular dilation in the systolic phase and decreased fractional shortening and the ejection fraction. Insulin-stimulated glucose uptake and proline-rich Akt substrate 40 phosphorylation were 41% (p < 0.001) and 45% (p < 0.05) lower, respectively, in cardiomyocytes from rats on the HFD. However, long-chain fatty acid (LCFA) uptake was 1.4-fold increased (p < 0.001) and LCFA esterification into triacylglycerols and phospholipids was increased 1.4- and 1.5-fold, respectively (both p < 0.05), in cardiomyocytes from HFD compared with LFD hearts. In the presence of the CD36 inhibitor sulfo-N-succinimidyloleate, LCFA uptake and esterification were similar in LFD and HFD cardiomyocytes. In HFD hearts CD36 was relocated to the sarcolemma, and basal phosphorylation of a mediator of CD36-trafficking, i.e. protein kinase B (PKB/Akt), was increased. CONCLUSIONS/INTERPRETATION: Feeding rats an HFD induced cardiac contractile dysfunction, which was accompanied by the relocation of CD36 to the sarcolemma, and elevated basal levels of phosphorylated PKB/Akt. The permanent presence of CD36 at the sarcolemma resulted in enhanced rates of LCFA uptake and myocardial triacylglycerol accumulation, and may contribute to the development of insulin resistance and diabetic cardiomyopathy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-007-0735-8) contains supplementary material, which is available to authorised users. Springer-Verlag 2007-07-18 2007-09 /pmc/articles/PMC2039861/ /pubmed/17639306 http://dx.doi.org/10.1007/s00125-007-0735-8 Text en © Springer-Verlag 2007
spellingShingle Article
Ouwens, D. M.
Diamant, M.
Fodor, M.
Habets, D. D. J.
Pelsers, M. M. A. L.
El Hasnaoui, M.
Dang, Z. C.
van den Brom, C. E.
Vlasblom, R.
Rietdijk, A.
Boer, C.
Coort, S. L. M.
Glatz, J. F. C.
Luiken, J. J. F. P.
Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification
title Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification
title_full Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification
title_fullStr Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification
title_full_unstemmed Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification
title_short Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification
title_sort cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated cd36-mediated fatty acid uptake and esterification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2039861/
https://www.ncbi.nlm.nih.gov/pubmed/17639306
http://dx.doi.org/10.1007/s00125-007-0735-8
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