Effects of Resveratrol on Muscle Inflammation, Energy Utilisation, and Exercise Performance in an Eccentric Contraction Exercise Mouse Model

Abstract

Eccentric contraction can easily cause muscle damage and an inflammatory response, which reduces the efficiency of muscle contraction. Resveratrol causes anti-inflammatory effects in muscles, accelerates muscle repair, and promotes exercise performance after contusion recovery. However, whether resveratrol provides the same benefits for sports injuries caused by eccentric contraction is unknown. Thus, we explored the effects of resveratrol on inflammation and energy metabolism. In this study, mice were divided into four groups: a control group, an exercise group (EX), an exercise with low-dose resveratrol group (EX + RES25), and an exercise with high-dose resveratrol group (EX + RES150). The results of an exhaustion test showed that the time before exhaustion of the EX + RES150 group was greater than that of the EX group. Tumour necrosis factor-α (Tnfα) mRNA expression was lower in the EX + RES150 group than in the EX group. The energy utilisation of the EX + RES150 group was greater than that of the EX + RES25 group in different muscles. High-dose resveratrol intervention decreased Tnfα mRNA expression and enhanced the mRNA expressions of sirtuin 1, glucose transporter 4, AMP-activated protein kinase α1, and AMP-activated protein kinase α2 in muscles. These results revealed that high-dose resveratrol supplementation can reduce inflammation and oxidation and improve energy utilisation during short-duration high-intensity exercise.

Keywords: anti-inflammation; downhill running; eccentric contraction; energy utilization; resveratrol.

Figure 1

Experimental design of short-term downhill training. NC: control (n = 6); EX: exercise (n = 6); EX + RES25: exercise with resveratrol 25 mg/kg (n = 6); EX + RES150: exercise with resveratrol 150 mg/kg (n = 6).

Figure 2

Exhaustion test in different groups. NC: control (n = 6); EX: exercise (n = 6); EX + RES25: exercise with resveratrol 25 mg/kg (n = 6); EX + RES150: exercise with resveratrol 150 mg/kg (n = 6). Data are presented as mean ± SEM. Data were analysed using one-way analysis of variance and a t-test followed by the Bonferroni multiple comparison test. Superscript letters (a and b) in columns denote a significant difference (p < 0.05).

Figure 3

Effects of resveratrol on (A) lactate dehydrogenase and (B) creatine kinase with eccentric exercise–induced muscle damage. NC: control (n = 6); EX: exercise (n = 6); EX + RES25: exercise with resveratrol 25 mg/kg (n = 6); EX + RES150: exercise with resveratrol 150 mg/kg (n = 6). Data are presented as mean ± SEM. Data were analysed using one-way analysis of variance and a t-test followed by the Bonferroni multiple comparison test. Superscript letters (a, b and c) in columns denote a significant difference (p < 0.05).

Figure 4

Effects of resveratrol on inflammatory cytokines (A) Tnfα and (B) IL-6 mRNA expression in (1) gastrocnemius muscle, (2) tibialis anterior muscle, and (3) soleus muscle during short-duration downhill running. mRNA expression was normalized to GAPDH and expressed as fold change relative to the control group. NC: control (n = 6); EX: exercise (n = 6); EX + RES25: exercise with resveratrol 25 mg/kg (n = 6); EX + RES150: exercise with resveratrol 150 mg/kg (n = 6). Data are presented as mean ± SEM. Data were analysed using one-way analysis of variance and a t-test followed by the Bonferroni multiple comparison test. Superscript letters (a and b) in columns denote a significant difference (p < 0.05).

Figure 5

Effects of resveratrol on energy utilization and antioxidative mRNA expression in gastrocnemius muscle during short-duration downhill running. (A) Sirt1 mRNA (B) Ampkα1 mRNA (C) Ampkα2 mRNA (D) Glut4 mRNA (E) Pgc1α mRNA. mRNA expression was normalized to GAPDH and is expressed in terms of fold change relative to the control group. NC: control (n = 6); EX: exercise (n = 6); EX + RES25: exercise with resveratrol 25 mg/kg (n = 6); EX + RES150: exercise with resveratrol 150 mg/kg (n = 6). Data are presented as mean ± SEM. Data were analysed using one-way analysis of variance and a t-test followed by the Bonferroni multiple comparison test. Superscript letters (a, b and c) in columns denote a significant difference (p < 0.05).

Figure 6

Effects of resveratrol on energy utilization and antioxidative mRNA expression in tibialis anterior muscle during short-duration downhill running training. (A) Sirt1 mRNA (B) Ampkα1 mRNA (C) Ampkα2 mRNA (D) Glut4 mRNA (E) Pgc1α mRNA. mRNA expression was normalized to GAPDH and is expressed in terms of fold change relative to the control group. NC: control (n = 6); EX: exercise (n = 6); EX + RES25: exercise with resveratrol 25 mg/kg (n = 6); EX + RES150: exercise with resveratrol 150 mg/kg (n = 6). Data are presented as mean ± SEM. Data were analysed using one-way analysis of variance and a t-test followed by the Bonferroni multiple comparison test. Superscript letters (a, b and c) in columns denote a significant difference (p < 0.05).

Figure 7

Effects of resveratrol on energy utilization and antioxidative mRNA expression in soleus muscle during short-duration downhill running training. (A) Sirt1 mRNA (B) Ampkα1 mRNA (C) Ampα2 mRNA (D) Glut4 mRNA (E) Pgc1α mRNA. mRNA expression was normalized to GAPDH and is expressed in terms of fold change relative to the control group. NC: control (n = 6); EX: exercise (n = 6); EX + RES25: exercise with resveratrol 25 mg/kg (n = 6); EX + RES150: exercise with resveratrol 150 mg/kg (n = 6). Data are presented as mean ± SEM. Data were analysed using one-way analysis of variance and a t-test followed by the Bonferroni multiple comparison test. Superscript letters (a, b and c) in columns denote a significant difference (p < 0.05).

Figure 8

Different gene expression in EX + RES150 and EX groups. (A) MA plot illustrating the distribution of upregulated and downregulated genes (coloured dots) for EX + RES150 group vs. EX group; (B) volcano plot illustrating significance and fold change of the up and downregulated genes (coloured dots) for EX + RES150 group vs. EX group.

Figure 9

Gene ontology (GO) analysis of EX + RES150 group vs. NC group. (A) GO analysis of biological process pathways for EX + RES150 group vs. EX group; (B) GO analysis of molecular function pathways for EX + RES150 group vs. EX group; (C) GO analysis of cellular component pathways for EX + RES150 group vs. EX group.