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Diabetologia
Published in: Diabetologia 9/2007

Open Access 01-09-2007 | Article

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

Authors: D. M. Ouwens, M. Diamant, M. Fodor, D. D. J. Habets, M. M. A. L. Pelsers, M. El Hasnaoui, Z. C. Dang, C. E. van den Brom, R. Vlasblom, A. Rietdijk, C. Boer, S. L. M. Coort, J. F. C. Glatz, J. J. F. P. Luiken

Published in: Diabetologia | Issue 9/2007

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Abstract

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.
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Metadata
Title
Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification
Authors
D. M. Ouwens
M. Diamant
M. Fodor
D. D. J. Habets
M. M. A. L. Pelsers
M. El Hasnaoui
Z. C. Dang
C. E. van den Brom
R. Vlasblom
A. Rietdijk
C. Boer
S. L. M. Coort
J. F. C. Glatz
J. J. F. P. Luiken
Publication date
01-09-2007
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 9/2007
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-007-0735-8

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