Abstract
BackgroundReprogramming of fast-to-slow myofiber switch can improve endurance capacity and alleviate fatigue. Accumulating evidence suggests that a muscle-specific microRNA, miR-499 plays a crucial role in myofiber type transition. In this study, we assessed the effects of natural flavonoid myricetin on exercise endurance and muscle fiber constitution, and further investigated the underlying mechanism of myricetin in vivo and in vitro.MethodsA total of 66 six-week-old male Sprague Dawley rats were divided into non-exercise or exercise groups with/without orally administered myricetin (50 or 150 mg/kg) for 2 or 4 weeks. Time-to-exhaustion, blood biochemical parameters, muscle fiber type proportion, the expression of muscle type decision related genes were measured. Mimic/ inhibitor of miR-499 were transfected into cultured L6 myotubes, the expressions of muscle type decision related genes and mitochondrial respiration capacity were investigated.ResultsMyricetin treatment significantly improved the time-to-exhaustion in trained rats. The enhancement of endurance capacity was associated with an increase of the proportion of slow-twitch myofiber in both soleus and gastrocnemius muscles. Importantly, myricetin treatment amplified the expression of miR-499 and suppressed the expression of Sox6, the down-stream target gene of miR-499, both in vivo and in vitro. Furthermore, inhibition of miR-499 overturned the effects of myricetin on down-regulating Sox6.ConclusionsMyricetin promoted the reprogramming of fast-to-slow muscle fiber type switch and reinforced the exercise endurance capacity. The precise mechanisms responsible for the effects of myricetin are not resolved but likely involve regulating miR-499/Sox6 axis.
Highlights
Skeletal muscle is composed of myofibers with different contractile and metabolic properties
Exercise showed no significant effects on the level of lactate (P > 0.05 vs. non-exercise group, Fig. 1c), while both low-dose (50 mg/kg) and high-dose (150 mg/kg) of myricetin treatments remarkably reduced the levels of lactate (P < 0.01, exercise training for 2 weeks (Ex-2)-MYR50 vs. Ex-2, Ex-2-MYR150 vs. Ex-2; P < 0.001, exercise training for 4 weeks (Ex-4)-MYR50 vs. Ex-4, Ex-4-MYR150 vs. Ex-4, Fig. 1c)
Inhibition of miR-499 overturned the effects of myricetin in L6 myotubes, indicating that miR-499 played a crucial role in the effects of Discussion In the present study, we found that natural flavonoid myricetin notably augmented endurance capacity of Sprague Dawley (SD) rats and increased the TTE treadmill running
Summary
Skeletal muscle is composed of myofibers with different contractile and metabolic properties. Slow-twitch fibers, known as type I myofiber, predominantly express β-MHC, display oxidative metabolism and high endurance [1]. MicroRNAs (miRNAs) represent a family of noncoding RNA of 21–22 nucleotides in length that regulate the expression of gene involved in developmental and cellular processes, such as skeletal muscle plasticity. Myosin-encoded miRNAs, known as MyomiRs, have the ability to regulate myosin switching and myofiber identity [6]. Encoded by intron 19 of Myh7b gene, miR-499 is co-expressed with β-MHC and almost. Reprogramming of fast-to-slow myofiber switch can improve endurance capacity and alleviate fatigue. Accumulating evidence suggests that a muscle-specific microRNA, miR-499 plays a crucial role in myofiber type transition. We assessed the effects of natural flavonoid myricetin on exercise endurance and muscle fiber constitution, and further investigated the underlying mechanism of myricetin in vivo and in vitro
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