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. Diabetologia (2007) 50:1938-1948 DOI 10.1007 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. 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.

Combinations of dietary factors were studied in relation to breast-cancer occurrence among 133 breast cancer cases and 289 population controls in The Netherlands. Dietary factors were classified according to their possible mechanism of action, i.e., relating either to the intestinal microflora (total fat, fiber, fermented milk products) or to the anti-oxidant hypothesis (beta-carotene, selenium and polyunsaturated fatty acids). From 6 interactions evaluated, the combination of high fiber intake and high intake of fermented milk products was the only one suggesting synergistic protection (age-and-fat-adjusted OR for interaction = 0.48, 95% confidence interval (CI) = 0.21 - 1.13). In order to estimate the extent to which the above dietary factors together might be related to breast cancer, subjects with a supposedly favorable dietary pattern (low fat intake, high fiber intake, high intake of fermented milk products; high intake of beta-carotene and selenium, low intake of polyunsaturated fatty acids) were compared with subjects with an unfavorable dietary pattern. This resulted in an age-adjusted odds ratio of 0.40 (95% CI = 0.14 - 1.15), which was largely attributable to the combination of low intake of fat and high intake of fermented milk products and fiber (age-adjusted OR = 0.33, 95% CI = 0.15 - 0.73). The other factors did not appreciably affect the odds ratio. These analyses show in a quantitative way that a dietary pattern which combines low intake of fat and high intake of fiber and fermented milk products might provide substantial protection against breast cancer.