Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification.
Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification.
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DOI：
10.1007/s00125-007-0735-8
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发表时间：
2007-09
期刊：
影响因子：
8.2
通讯作者：
Luiken, J. J. F. P.
中科院分区：
文献类型：
--
作者：
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.
关键词：
心脏底物利用的变化导致能量代谢的改变可能是糖尿病心肌病发生的基础。我们研究了心肌细胞底物的摄取和利用以及脂肪酸转位酶CD 36在高脂饮食（HFD）大鼠体内心脏功能中的作用。将大鼠暴露于HFD或低脂饮食（LFD）。通过超声心动图监测体内心脏功能。在分离的心肌细胞中测定底物摄取和利用。喂食HFD 8周可诱导收缩期左心室扩张，缩短率和射血分数降低。在接受HFD的大鼠心肌细胞中，胰岛素刺激的葡萄糖摄取和富含脯氨酸的Akt底物40磷酸化分别降低了41%（p < 0.001）和45%（p < 0.05）。然而，与LFD心脏相比，HFD心脏的心肌细胞中长链脂肪酸（LCFA）摄取增加了1.4倍（p < 0.001），LCFA酯化为三酰甘油和磷脂分别增加了1.4倍和1.5倍（均p < 0.05）。在存在CD 36抑制剂磺基-N-琥珀酰亚胺油酸酯的情况下，LFD和HFD心肌细胞中的LCFA摄取和酯化相似。在HFD心脏中，CD 36被重新定位到肌膜，并且CD 36-运输的介质即蛋白激酶B（PKB/Akt）的基础磷酸化增加。喂食HFD可诱导大鼠心脏收缩功能障碍，伴随着CD 36向肌膜的迁移，以及磷酸化PKB/Akt的基础水平升高。CD 36在肌膜上的永久存在导致LCFA摄取率和心肌三酰甘油积累率的增加，并可能导致胰岛素抵抗和糖尿病心肌病的发展。本文的在线版本（doi：10.1007/s 00125 -007-0735-8）包含补充材料，可供授权用户使用。
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). 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. 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. 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. 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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