Oral quercetin supplementation hampers skeletal muscle adaptations in response to exercise training

Abstract

We aimed to test exercise-induced adaptations on skeletal muscle when quercetin is supplemented. Four groups of rats were tested: quercetin sedentary, quercetin exercised, placebo sedentary, and placebo exercised. Treadmill exercise training took place 5 days a week for 6 weeks. Quercetin groups were supplemented with quercetin, via gavage, on alternate days throughout the experimental period. Sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α mRNA levels, mitochondrial DNA (mtDNA) content, and citrate synthase (CS) activity were measured on quadriceps muscle. Redox status was also quantified by measuring muscle antioxidant enzymatic activity and oxidative damage product, such as protein carbonyl content (PCC). Quercetin supplementation increased oxidative damage in both exercised and sedentary rats by inducing higher amounts of PCC (P < 0.001). Quercetin supplementation caused higher catalase (P < 0.001) and superoxide dismutase (P < 0.05) activity in the non-exercised animals, but not when quercetin is supplemented during exercise. Quercetin supplementation increased SIRT1 expression, but when quercetin is supplemented during exercise, this effect is abolished (P < 0.001). The combination of exercise and quercetin supplementation caused lower (P < 0.05) mtDNA content and CS activity when compared with exercise alone. Quercetin supplementation during exercise provides a disadvantage to exercise-induced muscle adaptations.

Quercetin supplementation does not enhance cerebellar mitochondrial biogenesis and oxidative status in exercised rats

“…This differs from what has previously been shown for the brain as a whole [15]. However, when supplemented during exercise, a pro-oxidant shift occurred by increasing PCC, as has already been described for brain and skeletal muscle tissue [14,15]. This can be explained by the "quercetin paradox," which suggests that the antioxidant effect of quercetin occurs at the first stage of supplementation; later on, quercetin metabolites become pro-oxidant agents [16,17].…”

“…Furthermore, polyphenols such as isoflavones, resveratrol, and quercetin target SIRT1 at the transcriptional level, which in turn increases PGC-1α mRNA levels [5,12,13]. In a previous study, we found that despite an increased PGC-1α mRNA level in skeletal muscle, mitochondrial content was not increased in exercised rats that were supplemented with quercetin, which can be explained by the unchanged SIRT1 expression [14]. It should be noted that similarly to data regarding the whole brain [15], quercetin supplementation during exercise also inhibits cellular adaptations related to mitochondrial biogenesis in rat cerebellums.…”

“…These effects seem to mimic those brought about by exercise in the mitochondrial content of skeletal muscle [8]. However, after a 6-week test of quercetin supplementation on exercised rats, mitochondrial content in skeletal muscle was compromised in response to lower SIRT1 transcription [14]. Furthermore, the brains of rats that consumed quercetin while exercising showed lower mitochondrial content as a result of the ablation of the SIRT1-PGC-1α axis [15].…”

“…The duration of the training was increased by 5 minutes every 2 days. The animals ran for 80 minutes on the last day of the fifth week and also throughout the last week of training [14]. The rats in the quercetin groups were supplemented via gavage (QU995; Quercegen Pharma, Newton, MA, USA) on alternate days during the experimental period.…”

“…Furthermore, the brains of rats that consumed quercetin while exercising showed lower mitochondrial content as a result of the ablation of the SIRT1-PGC-1α axis [15]. Furthermore, oxidative damage affected protein structures in the tissues of exercised rats [14,15]. Boots et al [16] described that metabolites (as a result of their antioxidant activity) changed to pro-oxidant agents, which in turn attacked protein structures [16,17].…”