title: Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation.
abstract: BACKGROUND
  Betaine (BET) is a component of many foods, including spinach and wheat. It is an essential osmolyte and a source of methyl groups. Recent studies have hypothesized that BET might play a role in athletic performance. However, BET effects on skeletal muscle differentiation and hypertrophy are still poorly understood.
  
  
  METHODS
  We examined BET action on neo myotubes maturation and on differentiation process, using C2C12 murine myoblastic cells. We used RT2-PCR array, Western blot and immunofluorescence analysis to study the BET effects on morphological features of C2C12 and on signaling pathways involved in muscle differentiation and hypertrophy.
  
  
  RESULTS
  We performed a dose-response study, establishing that 10 mM BET was the dose able to stimulate morphological changes and hypertrophic process in neo myotubes. RT2-PCR array methodology was used to identify the expression profile of genes encoding proteins involved in IGF-1 pathway. A dose of 10 mM BET was found to promote IGF-1 receptor (IGF-1 R) expression. Western blot and immunofluorescence analysis, performed in neo myotubes, pointed out that 10 mM BET improved IGF-1 signaling, synthesis of Myosin Heavy Chain (MyHC) and neo myotubes length.
  
  
  CONCLUSIONS
  Our findings provide the first evidence that BET could promote muscle fibers differentiation and increase myotubes size by IGF-1 pathway activation, suggesting that BET might represent a possible new drug/integrator strategy, not only in sport performance but also in clinical conditions characterized by muscle function impairment.
authors.forename: Pamela
authors.initials: P
authors.lastname: Senesi
authors.forename: Livio
authors.initials: L
authors.lastname: Luzi
authors.forename: Anna
authors.initials: A
authors.lastname: Montesano
authors.forename: Nausicaa
authors.initials: N
authors.lastname: Mazzocchi
authors.forename: Ileana
authors.initials: I
authors.lastname: Terruzzi
mesh_terms: D000818:Animals; D001622:Betaine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology*; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001622:Betaine; D007334:Insulin-Like Growth Factor I