Background 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. 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. Methods A 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. Results Myricetin 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. Conclusions Myricetin 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.

No abstract

The purpose of this study was to examine whether endogenous GLP-1 (glucagon-like peptide-1) could respond to exercise training in mice, as well as whether dihydromyricetin (DHM) supplementation could enhance GLP-1 levels in response to exercise training. After 2 weeks of exercise intervention, we found that GLP-1 levels were significantly elevated. A reshaped gut microbiota was identified following exercise, as evidenced by the increased abundance of Bifidobacterium, Lactococcus, and Alistipes genus, which are involved in the production of short-chain fatty acids (SCFAs). Antibiotic treatment negated exercise-induced GLP-1 secretion, which could be reversed with gut microbiota transplantation. Additionally, the combined intervention (DHM and exercise) was modeled in mice. Surprisingly, the combined intervention resulted in higher GLP-1 levels than the exercise intervention alone. In exercised mice supplemented with DHM, the gut microbiota composition changed as well, while the amount of SCFAs was unchanged in the stools. Additionally, DHM treatment induced intracellular cAMP in vitro and down-regulated the gene and protein expression of dipeptidyl peptidase-4 (DPP-4) both in vivo and in vitro. Collectively, the auxo-action of exercise on GLP-1 secretion is associated with the gut-microbiota-SCFAs axis. Moreover, our findings suggest that DHM interacts synergistically with exercise to enhance GLP-1 levels by stimulating cAMP and inhibiting DPP-4.

The study investigated the effect of pterostilbene (PTE) on intestinal glucose absorption and its underlying mechanisms in high-intensity swimming exercise (HISE)-treated mice. Male C57BL/6 mice were treated with PTE for 4 weeks and performed high-intensity swimming training in the last week. Intestinal epithelial cells (IECs) were pretreated with 0.5 and 1.0 μM PTE for 24 h before being incubated in hypoxia/reoxygenation condition. Intestinal glucose absorption was detected by using an oral glucose tolerance test and d-xylose absorption assay, and the levels of factors related to mitochondrial function and pyroptosis were measured via western blot analyses, cell mito stress test, and quantitative real-time polymerase chain reaction. In vivo and in vitro, the results showed that PTE attenuated HISE-induced intestinal glucose absorption dysfunction and pyroptosis in mice intestine. Moreover, PTE inhibited NLRP3 inflammasome and the mitochondrial homeostasis as well as the ROS accumulation in IEC in vitro. Additionally, knockdown of SIRT3, a major regulator of mitochondria function, by siRNA or inhibiting its activity by 3-TYP abolished the effects of PTE on pyroptosis, mitochondrial homeostasis, and ROS generation of IEC in vitro. Our results revealed that PTE could alleviate HISE-induced intestinal glucose absorption dysfunction associated with the inhibition of NLRP3 inflammasome-induced IECs pyroptosis.

An amendment to this paper has been published and can be accessed via the original article.