Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation

J Transl Med. 2013 Jul 19;11:174. doi: 10.1186/1479-5876-11-174.

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.

MeSH terms

  • Animals
  • Betaine / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Line
  • Cell Proliferation / drug effects
  • Dietary Supplements*
  • Insulin-Like Growth Factor I / metabolism*
  • Mice
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / cytology*
  • Myoblasts / cytology*
  • Myoblasts / drug effects
  • Myoblasts / metabolism
  • Signal Transduction / drug effects*

Substances

  • Betaine
  • Insulin-Like Growth Factor I