The role of L-type amino acid transporter 1 (Slc7a5) during in vitro myogenesis.

Satellite cells are required for muscle regeneration, remodeling, and repair through their activation, proliferation, and differentiation; however, how dietary factors regulate this process remains poorly understood. The L-type amino acid transporter 1 (LAT1) transports amino acids, such as leucine, into mature myofibers, which then stimulate protein synthesis and anabolic signaling. However, whether LAT1 is expressed on myoblasts and is involved in regulating myogenesis is unknown. The aim of this study was to characterize the expressional and functional relevance of LAT1 during different stages of myogenesis and in response to growth and atrophic conditions in vitro. We determined that LAT1 is expressed by C2C12 and human primary myoblasts, and its gene expression is lower during differentiation (P < 0.05). Pharmacological inhibition and genetic knockdown of LAT1 impaired myoblast viability, differentiation, and fusion (all P < 0.05). LAT1 protein content in C2C12 myoblasts was not significantly altered in response to different leucine concentrations in cell culture media or in two in vitro atrophy models. However, LAT1 content was decreased in myotubes under atrophic conditions in vitro (P < 0.05). These findings indicate that LAT1 is stable throughout myogenesis and in response to several in vitro conditions that induce muscle remodeling. Further, amino acid transport through LAT1 is required for normal myogenesis in vitro.

Sex-based comparisons of muscle cellular adaptations after 10 weeks of progressive resistance training in middle-aged adults.

Resistance training combined with adequate protein intake supports skeletal muscle strength and hypertrophy. These adaptations are supported by the action of muscle stem cells (MuSCs), which are regulated, in part, by fibro-adipogenic progenitors (FAPs) and circulating factors delivered through capillaries. It is unclear if middle-aged males and females have similar adaptations to resistance training at the cellular level. To address this gap, 27 (13 males, 14 females) middle-aged (40-64 yr) adults participated in 10 wk of whole body resistance training with dietary counseling. Muscle biopsies were collected from the vastus lateralis pre- and posttraining. Type II fiber cross-sectional area increased similarly with training in both sexes (P = 0.014). MuSC content was not altered with training; however, training increased PDGFRα+/CD90+ FAP content (P < 0.0001) and reduced PDGFRα+/CD90- FAP content (P = 0.044), independent of sex. The number of CD31+ capillaries per fiber also increased similarly in both sexes (P < 0.05). These results suggest that muscle fiber hypertrophy, stem/progenitor cell, and capillary adaptations are similar between middle-aged males and females in response to whole body resistance training.NEW & NOTEWORTHY We demonstrate that resistance training-induced increases in fiber hypertrophy, FAP content, and capillarization are similar between middle-aged males and females.

Nutritional Regulation of Muscle Stem Cells in Exercise and Disease: The Role of Protein and Amino Acid Dietary Supplementation.

Human skeletal muscle is a remarkedly plastic tissue that has a high capacity to adapt in response to various stimuli. These adaptations are due in part to the function of muscle-resident stem/progenitor cells. Skeletal muscle regeneration and adaptation is facilitated by the activation and expansion of muscle stem cells (MuSCs). MuSC fate is regulated by signals released from cells in their niche, such as fibro-adipogenic progenitors (FAPs), as well as a variety of non-cellular niche components. Sufficient dietary protein consumption is critical for maximizing skeletal muscle adaptation to exercise and maintaining skeletal muscle in disease; however, the role of dietary protein in altering MuSC and FAP responses to exercise in healthy populations and skeletal muscle disease states requires more research. The present review provides an overview of this emerging field and suggestions for future directions. The current literature suggests that in response to resistance exercise, protein supplementation has been shown to increase MuSC content and the MuSC response to acute exercise. Similarly, protein supplementation augments the increase in MuSC content following resistance training. Endurance exercise, conversely, is an area of research that is sparse with respect to the interaction of protein supplementation and exercise on muscle stem/progenitor cell fate. Initial evidence suggests that protein supplementation augments the early myogenic response to acute endurance exercise but does not enhance the MuSC response to endurance training. Resistance training increases the number of proliferating FAPs with no additional effect of protein supplementation. Future research should continue to focus on the nutritional regulation of skeletal muscle stem/progenitor cell fate paired with studies examining the effects of exercise on a variety of human populations.