Palmitic acid and myristic acid promote myogenesis through dual effects on myoblast cell cycle exit and myotube formation

Myogenic differentiation plays a vital role in embryonic muscle formation, postnatal muscle regeneration and repair processes. Exogenous fatty acids (FAs) influence physiological functions of skeletal muscle. Nevertheless, our grasp of how various types of FAs influence skeletal muscle differentiation remains limited and inconsistent. In this study, we comprehensively evaluated the effects of the six prevalent FAs on metabolism, proliferation, and differentiation of skeletal muscle precursor cells. We employed C2C12 myoblasts and treated them with three saturated FAs: palmitic acid (PA), stearic acid (SA), myristic acid (MA), as well as three unsaturated FAs: docosahexaenoic acid (DHA), oleic acid (OA), linoleic acid (LA). We found OA and LA facilitated proliferation of C2C12 cells through MAPK-ERK1/2 pathway, whereas DHA and MA had a mild inhibitory effect on this process. No significant effect on cell proliferation was noted with PA or SA treatment. Interestingly, both PA and MA unexpectedly enhanced myogenic differentiation, evidenced by promoting cell cycle exit through increased p21 levels, alongside myotube formation via upregulation of myogenin and MyHC by PI3K/Akt signaling pathway. In contrast, SA and all three unsaturated FAs considerably hindered myogenic differentiation. Collectively, these findings suggest PA and MA might serve as beneficial FAs to support skeletal muscle differentiation. Furthermore, even within the same categories of FAs, such as saturated and unsaturated, their effects on myogenesis differ and may even be contradictory. This observation challenges the traditional perceptions regarding FAs and provides a novel perspective for understanding the impact of different FAs on myogenesis.