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The mechanistic/mammalian target of rapamycin (mTOR) is a well-known serine/threonine kinase that activates muscle protein synthesis in response to anabolic conditions after exercise or nutrition intake. Rapamycin, a canonical inhibitor of mTOR complex 1 (mTORC1), induces mitochondrial dysfunction in addition to attenuating the muscle protein synthesis response. These findings suggest that mTORC1 contributes to mitochondrial homeostasis; however, the involvement of mTOR complex 2 (mTORC2) and the relationship between mTORC1 and mTORC2 are unclear. Therefore, this study was conducted to determine the role of the mTOR complex in mitochondrial function in skeletal muscle cells using rapamycin and AZD8055, as an ATP-competitive mTOR kinase inhibitor that inhibits both mTORC1 and mTORC2. AZD8055 treatment more significantly reduced the expression of proteins associated with mitochondrial oxidative phosphorylation, fusion, and fission, and decreased the respiratory capacity than rapamycin treatment. In conclusion, mTORC1 and mTORC2 cooperatively regulate mitochondrial protein expressions and respiratory function in skeletal muscle cells. [ABSTRACT FROM AUTHOR]

Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to elucidate the effect of early onset of exercise on muscle injury. Methods: Mice were divided into 3 groups, control group, injury group and exercise group. For injury group and exercise group, we forced micc to get muscle injury (eccentric-stimulation induced muscle injury). Then, for only exercise group, we let mice exercise (60 minutes swimming for 3 in every 4 days) after 7 days of muscle injury. All groups were sacrificed 21 days after muscle injury. Result and Discussion: we observed that the cross sectional area of the regenerating myofibers in exercise group was larger than that in injury group and the level of fibrosis in the exercise group was lower than that in injury group. Then, we measured mRNA level of collagenlα2 and collagen5α3, which are known to be fibrosis structural component. Collagen1α2 mRNA level are almost the same among 3 groups. On the other hand, in collagen5α3 mRNA level, exercise group showed less collagen5α3 mRNA level than injury group. Then, in order to reveal how exercise inhibits fibrosis, we measured mRNA level of TGF-β 1, which is a cytokine for promoting fibrosis. We observed that TGF-β 1 mRNA level of exercise group was less than that of injury group. Taken together, our data suggests that exercise improves healing process and exercise inhibit fibrosis via TGF-β 1 down regulation. [ABSTRACT FROM AUTHOR]

Purpose: Ammonia, one of the factors inducing fatigue, is transported by Rh b glycoprotein (Rhbg) and Rh c glycoprotein (Rhcg) in liver, kidney and other organs. The purpose of this study is examination of expression of Rhbg and Rhcg in skeletal muscle. Methods: Skeletal muscle samples (Soleus: Sol, Plantaris: Pia, Gastrocremius: Gas) were dissected from ICR mice (male, 8weeks old). Rhbg and Rhcg protein contents were analyzed by Western blot. Localization of Rhbg and Rhcg were analyzed by immunofluorescent microscopy. Myosin Heavy Chain (MHC) type composition of each muscles were measured by SDS-PAGE. Results: Rhbg and Rhcg protein much expressed in Sol than Pia and Gas. A positive correlation was found between MHC type I + II a/ II b and Rhbg/Rhcg expression. Immnofluorescent microscopy identified that Rhbg was colocalized with dystrophin, plasma membrane protein marker. On the other hand, staining for Rhcg showed colocalization with CD31 (vascular endothelial cell marker). Discussion: Ammonia transporters, both Rhbg and Rhcg, were rich in slow type fiber predominance muscle. Ammonia transporters may contribute in slow fiber than fast fiber. Rhbg and Rhcg localizations were different in types ofskeletal muscle. This result indicates that Rhbg and Rhbg have different role in skeletal muscle. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the effects of exercise on adult satellite cell conversion focusing at Wnt signaling, which plays important roles in lineage control during embryonic myogenesis and postnatal development. Methods: Male C57BL/6J mice ages 8 weeks (adult) and 24 months (aged) were used and divided into control group and runner group. Runner group mice were housed individually in cages equipped with a running wheel and performed voluntary wheel running for 4 weeks. After 4 weeks of exercise, mice were sacrificed and the gastrocnemius muscles were dissected out quickly from each mouse. Results: We demonstrated that voluntary wheel running exercise, which was a low-stress exercise, converted satellite cells to activated state due to accelerated Wnt signaling. Our analyses showed that upregulated canonical Wnt/b-catenin signaling directly modulated chromatin structures of both MyoD and Myf5 genes, resulting in increases in the mRNA expression of Myf5 and MyoD and the number of proliferative Pax7(+)Myf5(+) and Pax7(+)MyoD(+) cells in skeletal muscle. The effect of Wnt signaling on the activation of satellite cells, rather than Wnt-mediated fibrosis, was observed in both adult and aged mice. Discussion: These results indicate that exercise-stimulated extracellular Wnts play a critical role in the regulation of satellite cells in adult and aged skeletal muscle. [ABSTRACT FROM AUTHOR]

Endurance exercise (EE) mainly improves oxidative capacity, whereas high-intensity interval exercise (HIIE) also improves glycolytic capacity. There is growing evidence that suggests that combining EE with HIIE can lead to improved athletic performance and fitness outcomes compared with either form of exercise alone. This study aimed to elucidate whether the order in which EE and HIIE are performed in combined training affects oxidative metabolism and glycolysis in mouse skeletal muscle. Male ICR mice at 7 wk of age were divided into three groups: control (CON), EE-HIIE, and HIIE-EE. The total training period was 3 wk (3 times/week). Mice performed running on a treadmill as endurance exercise and swimming with a weight load of 10% of body weight as high-intensity interval exercise. EE before HIIE (EE-HIIE) improved running performance in the maximal EE capacity test (all-out test) and partly enhanced the expression levels of molecular signals involved in glycolysis compared with HIIE before EE (HIIE-EE). The order of exercise did not, however, impact the expression of proteins related to mitochondrial dynamics, including those involved in the morphological changes of mitochondria through repeated fusion and fission, as well as oxidative energy metabolism. The findings suggest that the order of exercise has no significant impact on the expression of proteins associated with glycolytic and oxidative energy metabolism. Nevertheless, our results indicate that the order of EE-HIIE may enhance running performance.

Skeletal muscles contain stem cells called satellite cells, which are essential for muscle regeneration. The population of satellite cells declines with aging and the incidence of pathological conditions such as muscular dystrophy. There is increasing evidence that metabolic switches and mitochondrial function are critical regulators of cell fate decision (quiescence, activation, differentiation, and self-renewal) during myogenesis. Thus, monitoring and identifying the metabolic profile in live cells using the Seahorse XF Bioanalyzer could provide new insights on the molecular mechanisms governing stem cell dynamics during regeneration and tissue maintenance. Here we described a method to assess mitochondrial respiration (oxygen consumption rate) and glycolysis (ECAR) in primary murine satellite cells, multinucleated myotubes, and C2C12 myoblasts., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Aging is an inevitable physiological process that leads to the dysfunction of various tissues, and these changes may contribute to certain diseases, and ultimately death. Recent research has discovered biological pathways that promote aging. This review focuses on Wnt signaling, Wnt is a highly conserved secreted signaling molecule that plays an essential role in the development and function of various tissues, and is a notable factor that regulates aging. Although Wnt signaling influences aging in various tissues, its effects are particularly prominent in neuronal tissue and skeletal muscle. In neuronal tissue, neurogenesis is attenuated by the downregulation of Wnt signaling with aging. Skeletal muscle can also become weaker with aging, in a process known as sarcopenia. A notable cause of sarcopenia is the myogenic-to-fibrogenic trans-differentiation of satellite cells by excessive upregulation of Wnt signaling with aging, resulting in the impaired regenerative capacity of aged skeletal muscle. However, exercise is very useful for preventing the age-related alterations in neuronal tissue and skeletal muscle. Upregulation of Wnt signaling is implicated in the positive effects of exercise, resulting in the activation of neurogenesis in adult neuronal tissue and myogenesis in mature skeletal muscle. Although more investigations are required to thoroughly understand age-related changes and their biological mechanisms in a variety of tissues, this review proposes exercise as a useful therapy for the elderly, to prevent the negative effects of aging and maintain their quality of life.

Skeletal muscle has a high degree of plasticity. The mass of skeletal muscle maintains owing to muscle protein synthesis and the regeneration by satellite cells. Skeletal muscle atrophy with aging (sarcopenia) is developed by decline of muscle protein synthesis and dysfunction of satellite cells. It is urgently necessary for today's highly aged society to elucidate the mechanism of sarcopenia and to establish prevention measure. This review shows that the positive effects of "exercise" on muscle protein synthesis and satellite cell function including their main molecular mechanism.