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Oleanolic acid (OA) is a pentacyclic triterpene with reported protective effects against various diseases, including diabetes, hepatitis, and different cancers. However, the effects of OA on obesity‐induced muscle atrophy remain largely unknown. This study investigated the effects of OA on skeletal muscle production and proliferation of C2C12 cells. We report that OA significantly increased skeletal muscle mass and improved glucose intolerance and insulin resistance. OA inhibited dexamethasone (Dex)‐induced muscle atrophy in C2C12 myoblasts by regulating the PI3K/Akt signaling pathway. In addition, it also inhibited expression of MuRF1 and Atrogin1 genes in skeletal muscle of obese mice suffering from muscle atrophy, and increased the activation of PI3K and Akt, thereby promoting protein synthesis, and eventually alleviating muscle atrophy. Taken together, these findings suggest OA may have potential for the prevention and treatment of muscle atrophy. [ABSTRACT FROM AUTHOR]

Fgf21 has been identified as playing a regulatory role in muscle growth and function. Although the mechanisms through which endurance training regulates skeletal muscle have been widely studied, the contribution of Fgf21 remains poorly understood. Here, muscle size and function were measured, and markers of fiber type were evaluated using immunohistochemistry, immunoblots, or qPCR in endurance-exercise-trained wild-type and Fgf21 KO mice. We also investigated Fgf21-induced fiber conversion in C2C12 cells, which were incubated with lentivirus and/or pathway inhibitors. We found that endurance exercise training enhanced the Fgf21 levels of liver and GAS muscle and exercise capacity and decreased the distribution of skeletal muscle fiber size, and fast-twitch fibers were observed converting to slow-twitch fibers in the GAS muscle of mice. Fgf21 promoted the markers of fiber-type transition and eMyHC-positive myotubes by inhibiting the TGF-β1 signaling axis and activating the p38 MAPK signaling pathway without apparent crosstalk. Our findings suggest that the transformation and function of skeletal muscle fiber types in response to endurance training could be mediated by Fgf21 and its downstream signaling pathways. Our results illuminate the mechanisms of Fgf21 in endurance-exercise-induced fiber-type conversion and suggest a potential use of Fgf21 in improving muscle health and combating fatigue. [ABSTRACT FROM AUTHOR]

When skeletal muscle is damaged, satellite cells (SCs) are activated to proliferate rapidly and fuse with the damaged muscle fibers to form new muscle fibers, thereby promoting muscle growth and remodeling and repair of trauma. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration. Therefore, we hypothesized that, when muscles are injured, myoblast‐derived exosomes may regulate muscle repair and regeneration. Here, we investigated the underlying mechanism by applying C2C12‐derived exosomes to injured mouse skeletal muscles. The expression levels of skeletal muscle regeneration factors paired box 7 and lipid‐promoting factor peroxisome proliferator‐activated receptor γ were upregulated, whereas the expression levels of fibrosis factors collagen‐1 and α‐smooth muscle actin decreased. The expression of proliferating cell nuclear antigen was elevated after applying C2C12‐derived exosomes to SCs. Application of C2C12‐derived exosomes to fibro‐adipogenic progenitors resulted in an increase in peroxisome proliferator‐activated receptor γ expression and adipogenesis capacity, whereas α‐smooth muscle actin expression and fibrosis capacity decreased. Analysis of the transcriptome and proteome of SCs after treatment with exosomes showed the involvement of multiple biological processes, including proliferation and differentiation of SCs, muscle regeneration, skeletal muscle atrophy, and the inflammatory response after muscle injury. Hence, our data suggest that C2C12‐derived exosomes can promote the regeneration of skeletal muscle fibers, accelerate the production of fat from damaged muscles, inhibit the fibrosis of damaged muscles, and accelerate injury repair, which is related to exosome‐mediated regulation of the proliferation of SCs, differentiation of fibro‐adipogenic progenitors, and modulation of SC mRNA expression and protein formation and decomposition. [ABSTRACT FROM AUTHOR]

As a newly discovered muscle factor secreted by skeletal muscle cells, irisin is a polypeptide fragment formed from hydrolysis of fibronectin type Ⅲ domain-containing protein 5 (FNDC5). Irisin can promote beigeing of white adipose tissue (WAT) and regulate glucose and lipid metabolisms. However, the functions of irisin in skeletal muscle development remain largely unknown. In order to characterize the expression of irisin, this study investigated the expression of irisin precursor FNDC5 in myoblasts and skeletal muscles during different developmental stages of SPF mice. The Western blot, quantitative real-time PCR (qRT-PCR), and immunofluorescence assay results showed that FNDC5 was expressed in all the developmental stages of myoblasts and gastrocnemius, but its expression differed at different stages. FNDC5 protein exhibited the highest expression in gastrocnemius of sexually mature mice, followed by elderly mice and adolescent mice, and it displayed the lowest expression in pups. Additionally, FNDC5 protein was mainly expressed in cytoplasm, and it had the highest expression in primary myoblasts, followed by the myotubes with the lowest expression in C2C12 myogenic cells. Overall, FNDC5 was mainly expressed in cytoplasm and extracellular matrix with different expression levels at different developmental stages of skeletal muscle cells and tissues in mice. This study will provide new strategies for promoting skeletal muscle development and treating muscle- and metabolism-related disease by using irisin. • High expression of FNDC5 in skeletal muscle of sexually mature mice. • FNDC5 is differentially expressed at different stages of myoblast differentiation. • FNDC5 is localized in the cytoplasm and extracellular matrix of skeletal muscle cells and not in the nucleus. [ABSTRACT FROM AUTHOR]