Tomatidine Exposure During Early Myogenesis Promotes Hypertrophy of C2C12 Muscle Cells Through Increased Nuclei Accretion

Abstract

During myogenesis or myofiber regeneration, a proliferating muscle cell must leave the cell cycle, commit to differentiate, and fuse to neighboring myoblasts to create multinucleated myotubes, and eventually mature myofibers. These stages can be manipulated by exogenous factors including signaling molecules, mechanical cues, and nutrient supplementation. Supplementation with bioactives, such as tomatidine, can improve aspects of skeletal muscle health when evaluated using in vitro and in vivo models. In this study, a phenotypic characterization of the effects of tomatidine supplementation during proliferation, early maturation and differentiation, was undertaken in C2C12 muscle cells, cultured in growth medium, or alternatively induced to differentiate in medium supplemented with 10 µM tomatidine, for up to 4 days. Real‐time impedance assays indicated tomatidine slowed C2C12 proliferation after 3 days of supplementation. Tomatidine supplementation from the onset of differentiation induced myotube hypertrophy within the first 48 h of maturation. Tomatidine‐induced hypertrophy was driven by increased myonuclei fusion in developing myotubes with a concomitant increase in protein synthesis. Taken together, tomatidine's growth promoting effects on skeletal muscle cells identify its therapeutic potential for enhancing muscle regeneration and repair, by mechanisms that improve myofiber maturation and function.