Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
Cardiovascular Research Institute, National University Health System, National University of Singapore, Singapore; and.
Am J Physiol Heart Circ Physiol. 2016 Jul 1;311(1):H1-H10. doi: 10.1152/ajpheart.00809.2015. Epub 2016 May 6.
High-fat, low-carbohydrate Diet (HFLCD) impairs the myocardial response to ischemia-reperfusion, but the underlying mechanisms remain elusive. We sought to determine the magnitude of diet-induced alterations in intrinsic properties of the myocardium (including insulin sensitivity and substrate oxidation) and circulating substrate and insulin differences resulting from diet, leading to this impaired response. Rats were fed HFLCD (60% kcal from fat/30% protein/10% carbohydrate) or control diet (CONT) (16%/19%/65%) for 2 wk. Isolated hearts underwent global low-flow ischemia followed by reperfusion (I/R). Carbon-13 NMR spectroscopy was used to determine myocardial substrate TCA cycle entry. Myocardial insulin sensitivity was assessed as dose-response of Akt phosphorylation. There was a significant effect of HFLCD and I/R with both these factors leading to an increase in free fatty acid (FFA) oxidation and a decrease in carbohydrate or ketone oxidation. Following I/R, HFLCD led to decreased ketone and increased FFA oxidation; the recovery of left ventricular (LV) function was decreased in HFLCD and was negatively correlated with FFA oxidation and positively associated with ketone oxidation. HFLCD also resulted in reduced insulin sensitivity. Under physiologic ranges, there were no direct effects of buffer insulin and ketone levels on oxidation of any substrate and recovery of cardiac function after I/R. An insulin-ketone interaction exists for myocardial substrate oxidation characteristics. We conclude that the impaired recovery of function after ischemia-reperfusion with HFLCD is largely due to intrinsic diet effects on myocardial properties, rather than to diet effect on circulating insulin or substrate levels.
高脂肪、低碳水化合物饮食（HFLCD）会损害心肌对缺血再灌注的反应，但潜在机制仍不清楚。我们试图确定饮食引起的心肌内在特性（包括胰岛素敏感性和底物氧化）以及循环底物和胰岛素差异的程度，这些差异导致了这种反应受损。大鼠喂食 HFLCD（60%来自脂肪/30%蛋白质/10%碳水化合物）或对照饮食（CONT）（16%/19%/65%）2 周。分离的心脏经历了全球低流量缺血，然后再灌注（I/R）。使用 13C-NMR 光谱法测定心肌底物三羧酸（TCA）循环进入。心肌胰岛素敏感性作为 Akt 磷酸化的剂量反应来评估。HFLCD 和 I/R 均有显著影响，这两个因素都导致游离脂肪酸（FFA）氧化增加，碳水化合物或酮体氧化减少。在 I/R 后，HFLCD 导致酮体减少和 FFA 氧化增加；HFLCD 下 LV 功能的恢复减少，与 FFA 氧化呈负相关，与酮体氧化呈正相关。HFLCD 还导致胰岛素敏感性降低。在生理范围内，缓冲胰岛素和酮体水平对任何底物的氧化和 I/R 后心脏功能的恢复没有直接影响。胰岛素-酮体相互作用存在于心肌底物氧化特性中。我们得出结论，HFLCD 缺血再灌注后功能恢复受损主要是由于饮食对心肌特性的内在影响，而不是饮食对循环胰岛素或底物水平的影响。
