Impact of high-fat, low-carbohydrate diet on myocardial substrate oxidation, insulin sensitivity, and cardiac function after ischemia-reperfusion

Abstract

Liu J, Wang P, Douglas SL, Tate JM, Sham S, Lloyd SG. Impact of high-fat, low-carbohydrate diet on myocardial substrate oxidation, insulin sensitivity, and cardiac function after ischemia-reperfusion. Am J Physiol Heart Circ Physiol 311: H1-H10, 2016. First published May 6, 2016; doi:10.1152/ajpheart.00809.2015.-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 insulinketone 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. diet; myocardial ischemia-reperfusion injury; insulin; metabolism NEW & NOTEWORTHYThe substrate oxidation and response to I/R are more dependent on diet than on physiologic range changes in circulating substrate and insulin. This was associated with altered insulin sensitivity. After I/R, there was a positive (with ketone) and negative (with FFA) correlation between recovery of function and substrate oxidation.HIGH-FAT, LOW-CARBOHYDRATE DIETS (HFLCD S ) are used by many people in an effort to lose weight. The effect of such diets on cardiovascular health has been the subject of intense investigation. Population studies evaluating the impact of HFLCD on cardiovascular clinical outcomes have provided a range of results, with some finding favorable changes in cardiovascular disease risk factors (9, 35, 37), and others showing an increased risk of adverse outcomes in both animal (29) and human studies, including in the setting of myocardial infarction (23). Consistent with this latter finding, we have p...

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