Lycopene Increases Skeletal Muscle Mass by Promoting Myoblast Differentiation

Muscle differentiation is a necessary process for the growth, development and regeneration of skeletal muscles. Lycopene has been extensively documented to play a critical role in promoting mitochondrial biogenesis and energy metabolism in skeletal muscle. However, the role of lycopene, as a nutrient-active compound, in the process of muscle differentiation has not yet been reported. Therefore, this study aimed to assess the effects of supplementation with lycopene on skeletal muscle differentiation in vivo and in vitro, and investigate its potential mechanism. Results demonstrated that lycopene-fed mice showed markedly increased gastrocnemius muscle (GAS) mass and myofiber size. Lycopene promoted muscle protein synthesis and upregulated the expression levels of myogenic regulatory factors such as MyoD (myogenic determining factor) and MyoG (myogenin) in mice and in C2C12 cells, accompanied by promoted myotube formation during cell differentiation. Transcriptome sequencing analysis revealed that lycopene-induced promotion of muscle differentiation was associated with enhanced activity in the estrogen signaling pathway, as evidenced by upregulated expression levels of ERα in both mice and myoblasts. Furthermore, pharmacological inhibition or ERα specific-knockdown was used to analyze its function in muscle differentiation. Results found that ERα suppression effectively hindered the formation of myotubes and abolished the pro-differentiation effects of lycopene. Taken together, these findings suggested that lycopene exhibited beneficial effects on myoblast differentiation contributing to increased muscle mass.