Cell culture study using C2C12 and L6 cell lines representing different metabolic muscle fiber types to examine MOTS-c's effects on fiber differentiation, metabolic reprogramming, and mitochondrial function across oxidative and glycolytic fiber phenotypes. Characterizes fiber-type-specific MOTS-c biology. Provides foundational in vitro evidence for MOTS-c's differential effects across muscle fiber types—informing whether MOTS-c's therapeutic benefits in sarcopenia, exercise performance, and metabolic disease may depend on the predominant fiber type composition of target muscle groups.
Abstract
BACKGROUND/AIMS: MOTS-c belongs to a group of mitochondrial peptides involved in metabolic processes in the body. This peptide has garnered increasing attention since its discovery in 2015 because of its potential to ameliorate metabolic parameters in animals with diabetes or insulin resistance. MOTS-c is involved in muscle metabolism; however, little is known about its role in fiber differentiation.
METHODS: We conducted a study to explore the effect of MOTS-c on cellular processes using the C2C12 and L6 cell lines, representing different metabolic types of muscle fibers. The research methods were real-time PCR, Western blot, and lipid accumulation measurement.
RESULTS: Notably, our investigations revealed that MOTS-c increased the survival of C2C12 cells at doses of 10 and 100 nM (p<0.01) and stimulated the phosphorylation of extracellular signal-regulated kinase within 5 min of incubation (p<0.05). Remarkably, these effects were not observed in L6 cells; however, both cell lines showed a reduced rate of proliferation. Furthermore, MOTS-c promotes the differentiation of C2C12 cells by increasing the expression of muscle regulatory factors, but it does not produce such an effect in L6 cells. Additionally, cells were treated with physiological concentrations of free fatty acids and MOTS-c, unveiling an augmentation in lipid accumulation observed in L6 cells and a decrease in lipid accumulation in C2C12 cells.
CONCLUSION: In conclusion, our findings have suggested a diverse response to MOTS-c depending on the type of muscle fibers, particularly in the domains of survival, cell differentiation, and lipid accumulation.