Betaine (BET) is found in various plant and animals. BET participates in the methionine cycle and it is a precursor of S-adenosylmethionine (SAM). SAM is a direct methyl donor in proteins synthesis and DNA methylation. Myogenesis requires the coordinated activity of transcription factors (MRFs) and DNA methylation pattern modifications. Previous studies have hypothesized that BET supplementation may improve muscle endurance in human. However, BET effect on muscle formation remains unknown.

In this work we study BET action during myogenesis in C2C12 cell model. We investigated possibly BET hypertrophy effects on the late phase of differentiation (72h): C2C12 were treated with BET (10 mM) for different times (5, 10, 20, 30 min and 4, 8, 24 hours). BET was not added to medium in basal control. By RT-PCR array and Western Blot analysis we observed that BET actives IGF-1 pathway and increases cytoskeletal proteins content. Immunofluorescence analysis showed that BET induces morphological changes indicating the start of hypertrophy process.

We evaluated BET role on skeletal muscle differentiation at 8, 24, 48,72 and 96 hours. MRFs expression analysis shown that BET promotes myogenesis.

Our results demonstrate that BET influences myogenesis by activation of IGF1 pathway. BET action on myogenesis might provide the clue for a possible new drug/integrator strategy for clinical conditions characterized by muscle function impairment.