Improvements in skeletal muscle strength and cardiac function induced by resveratrol during exercise training contribute to enhanced exercise performance in rats

Abstract

Exercise training (ET) improves endurance capacity by increasing both skeletal muscle mitochondrial number and function, as well as contributing to favourable cardiac remodelling.Interestingly, some of the benefits of regular exercise can also be mimicked by the naturally occurring polyphenol, resveratrol (RESV). However, it is not known whether RESV enhances physiological adaptations to ET. To investigate this, male Wistar rats were randomly assigned to a control chow diet or a chow diet that contained RESV (4 g kg⁻¹ of diet) and subsequently subjected to a programme of progressive treadmill running for 12 weeks. ET-induced improvements in exercise performance were enhanced by 21% (P <0.001) by the addition of RESV to the diet. In soleus muscle, ET+RESV increased both the twitch (1.8-fold; P <0.05) and tetanic(1.2-fold; P <0.05) forces generated during isometric contraction, compared to ET alone. In vivo echocardiography demonstrated that ET+RESV also increased the resting left ventricular ejection fraction by 10% (P <0.05), and reduced left ventricular wall stress compared to ET alone.These functional changes were accompanied by increased cardiac fatty acid oxidation (1.2-fold;P <0.05) and favourable changes in cardiac gene expression and signal transduction pathways that optimized the utilization of fatty acids in ET+RESV compared to ET alone. Overall, our findings provide evidence that the capacity for fatty acid oxidation is augmented by the addition of RESV to the diet during ET, and that this may contribute to the improved physical performance of rats following ET.

Figure 1. Experimental design

Following acclimation to the treadmill, 10-week-old male Wistar rats were randomly divided into four groups, which included sedentary rats or exercise trained (ET; level treadmill running 20 m min⁻¹ for 60 min, 5 days week⁻¹ for 12 weeks) rats that received control AIN-93G diet (Control) or the AIN-93G diet supplemented with resveratrol (RESV; 4 g RESV/kg food). Glucose tolerance test (GTT). Insulin tolerance test (ITT). Rats were subjected to experimental procedures at the indicated time points.

Figure 2. Resveratrol (RESV) improves the endurance capacity of exercise-trained (ET) rats

A, body weight. B and C, time to exhaustion (B) and distance run (C) during a treadmill exercise test after the 12 weeks of ET. D and E, twitch and tetanic forces in the tibialis anterior (TA) muscle (D) and soleus muscle (E). F and G, the fatigue index (F) and SAG ratio (G) during isometric muscle contractions. Data are presented as the mean ± SEM of n = 10 rats. Significant difference: *P < 0.05 Control vs. RESV; §P < 0.05 Sedentary vs. ET using a two-way ANOVA and Bonferroni post hoc test.

Figure 3. Resveratrol (RESV) improves the cardiac function of exercise-trained (ET) rats

Following 12 weeks of exercise training, in vivo cardiac function was measured by echocardiography. A, cardiac ejection fraction. B, intraventricular relaxation time (IVRT). C, the E-wave/A-wave ratio. D, left ventricular (LV) posterior wall (LVPW) thickness. E, LV end diastolic (LVED) volume. F, LV end systolic (LVES) volume. G, stroke volume. H, LV wall stress. Data are presented as the mean ± SEM of n = 6 rats. Significant difference: *P < 0.05 Control vs. RESV; §P < 0.05 Sedentary vs. ET using a two-way ANOVA and Bonferroni post hoc test.

Figure 4. Resveratrol (RESV) improves whole-body glucose homeostasis and fatty acid oxidation in exercise trained (ET) rats

A and B, glucose (A) and insulin (B) tolerance tests. C and D, oxygen consumption () (C) and respiratory exchange ratio (RER) (D) were measured by indirect calorimetry. E and F, the amount of whole-body fat (E) and glucose oxidation (F) was calculated from the calorimetry data. G, food consumption was measured over a 24 h period. H, physical activity was monitored by dual axis detection using infra-red photocell technology over a 24 h period. Data are presented as the mean ± SEM of n = 6 rats. Significant difference: *P < 0.05 ET + Control vs. ET + RESV using a Student's t test.

Figure 5. Resveratrol (RESV) increases cardiac performance and elevates fatty acid oxidation in the isolated perfused working hearts of exercise trained (ET) rats

Cardiac function was measured in ex vivo perfused working rat hearts at both normal and high workload conditions. A, heart rate (HR) × peak systolic pressure (PSP). B, left-ventricular developed pressure (LVDP). C, coronary flow. D, cardiac work. E and F, glucose (E) and palmitate (F) oxidation rates were measured in perfused hearts at both normal and high workloads. Data are presented as the mean ± SEM of n = 6 hearts in each group. Significant difference *P < 0.05 ET + Control vs. ET + RESV; §P < 0.05 Normal vs. High Workload using a two-way ANOVA and Bonferroni post hoc test.

Figure 6. Resveratrol (RESV) modulates cardiac energy metabolism in exercise trained (ET) rats via altered signal transduction pathways and increased mitochondrial function

Immunoblot analysis was performed on homogenates of hearts from ET + Control and ET + RESV Wistar rats. A, levels of phosphorylated threonine-172 AMPK (P-AMPK) were quantified by densitometry and normalized against total AMPK. B, levels of phosphorylated serine-79 ACC (P-ACC) were quantified by densitometry and normalized against total ACC. C, levels of PGC-1α normalized against tubulin. D, levels of electron transport chain complexes compared to tubulin. E, citrate synthase assay. F, cardiac triacylglycerol levels. Values are the mean ± SEM of n = 6 rats in each group. *Significant difference (P < 0.05) between ET + Control and ET + RESV rats using a Student's t-test.