High-fat, low-carbohydrate diet promotes arrhythmic death and increases myocardial ischemia-reperfusion injury in rats

Abstract

High-fat, low-carbohydrate diets (HFLCD) are often eaten by humans for a variety of reasons, but the effects of such diets on the heart are incompletely understood. We evaluated the impact of HFLCD on myocardial ischemia/reperfusion (I/R) using an in vivo model of left anterior descending coronary artery ligation. Sprague-Dawley rats (300 g) were fed HFLCD (60% calories fat, 30% protein, 10% carbohydrate) or control (CONT; 16% fat, 19% protein, 65% carbohydrate) diet for 2 wk and then underwent open chest I/R. At baseline (preischemia), diet did not affect left ventricular (LV) systolic and diastolic function. Oil red O staining revealed presence of lipid in the heart with HFLCD but not in CONT. Following I/R, recovery of LV function was decreased in HFLCD. HFLCD hearts exhibited decreased ATP synthase and increased uncoupling protein-3 gene and protein expression. HFLCD downregulated mitochondrial fusion proteins and upregulated fission proteins and store-operated Ca(2+) channel proteins. HFLCD led to increased death during I/R; 6 of 22 CONT rats and 16 of 26 HFLCD rats died due to ventricular arrhythmias and hemodynamic shock. In surviving rats, HFLCD led to larger infarct size. We concluded that in vivo HFLCD does not affect nonischemic LV function but leads to greater myocardial injury during I/R, with increased risk of death by pump failure and ventricular arrhythmias, which might be associated with altered cardiac energetics, mitochondrial fission/fusion dynamics, and store-operated Ca(2+) channel expression.

A low-carbohydrate high-fat diet decreases lean mass and impairs cardiac function in pair-fed female C57BL/6J mice

“…Similar cardiac alterations have been reported in obese mice fed a long-term high-fat diet [30]. However, in a 2-week study on rats no change in CD36 was reported, making the duration of diet intake interesting [31]. In the present study the expression of the gene encoding natriuretic protein A (ANP) was significantly lower in the LCHF group.…”

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

“…This effect is not entirely due to the effect on glucose oxidation, since it is independent of its effect on glucose uptake in the postischemic isolated working rat heart (48). The observed decrease in Akt phosphorylation in HFLCD under I/R, with no change in CHO oxidation compared with CONT diet, is consistent with our previous work finding that HFLCD did not alter expression of glucose uptake (GLUT4) and glucose oxidation genes under I/R (25). Thus the cardioprotective effects of insulin, and its impact on glucose uptake, appear to be at least partly uncoupled.…”

“…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 previously demonstrated that HFLCD (when eaten prior to experimental infarction) induced lower recovery of cardiac function, larger infarct size, and increased risk of death by pump failure and ventricular arrhythmias following coronary ligation myocardial ischemia-reperfusion (25). However, the mechanisms causing these impaired responses are not fully known.…”

“…Adult male Sprague-Dawley rats 300 Ϯ 10 g (Taconic Farms, Hudson, NY) were fed one of two diets, each of which was designed to be similar to ones used by humans for weight loss: HFLCD [60% calories from fat/30% from protein/10% from carbohydrate, a relatively high-protein content (30% of kcals), and very high amount of saturated (40%) and monounsaturated (40%) fat designed to be similar to the induction phase of the Atkins diet for humans (10) (TestDiet 5TSY, Richmond, IN)] or a low-fat control diet (CONT) (16/19/65%; TestDiet 5TJM). The detailed components of the diets, including proportions of saturated, mono-and polyunsaturated fats as well as n-3 and n-6 polyunsaturated fatty acids have been described previously (24,25). Animals were fed the diets for 14 days prior to performing perfusion experiments.…”

Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

“…Previous studies have revealed that HFD promoted arrhythmic death and increased myocardial ischemia-reperfusion injury in rats [30]. Moreover, other studies also detected increased vulnerability of atrial arrhythmia and impaired conduction velocity in HFD mice [31].…”