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

Abstract

BackgroundBetaine (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.MethodsWe 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.ResultsWe 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.In addition, we investigated BET role on myoblasts proliferation and differentiation. During proliferation, BET did not modify C2C12 proliferative rate, but promoted myogenic induction, enhancing MyoD protein content and cellular elongation. During differentiation, BET caused an increase of muscle-specific markers and IGF-1 R protein levels.ConclusionsOur 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.

Methyl donors dietary supplementation to gestating sows diet improves the growth rate of offspring and is associating with changes in expression and DNA methylation of insulin‐like growth factor‐1 gene

“…The insulin‐like growth factor‐1 (IGF‐1) is a well‐known regulator for foetal development and postnatal growth (Hellström et al., ). The growth‐promoting effects of MD on foetus are thought to be mediated through IGF‐1 (Apicella et al., ; Lee, Kim, Park, & Kang, ; Senesi, Luzi, Montesano, Mazzocchi, & Terruzzi, ). In fact, the IGF‐1 gene promoters and coding regions contain multiple CG sites that are subjected to differential methylation (Fu, Yu, Callaway, Lane, & Mcknight, ; Zhao, Yang, Hu, Dong, & Zhao, ).…”

Betaine promotes cell differentiation of human osteoblasts in primary culture

“…In particular, it has been shown that BET enhances neo myotubes formation and differentiation while promoting IGF-I gene and protein expressions in C2C12 murine myoblasts [6], a model of skeletal muscle development [7]. IGF-I has long been known to play a role not only in muscle hypertrophy but even in bone strength [8, 9].…”

A Thermolabile Aldolase A Mutant Causes Fever-Induced Recurrent Rhabdomyolysis without Hemolytic Anemia

“…Also, they develop a system of defenses that represent an excellent example of redox balance maintenance [24]. Interestingly, we showed that protein and catalytic breakdown can be reversed by arginine but not by glycerol, benzylhydantoin and betaine which all might act as a chaperone as recently proposed for unrelated metabolic disorders [25]–[27]. Also, another mechanism may be proposed concerning the effective role of L-arginine on aldolase A activity, namely its antioxidant function via increased NO formation and reduced release of superoxide.…”

“…Three other chaperons (sigma) were also tested, glycerol (100 mM) [25] for 10 days, betaine (10 and 50 mM) [26], [27] and benzylhydantoin (130 µM) for 3 days. Uniformly stable isotope labeled (U- 13 C 5 ) glutamine or (U- 13 C 6 ) arginine (Eurisotop, Saint-Aubin, France) were provided to myoblasts (1 mM) in the presence of glucose (2.5 mM) and incubated without serum for 6 hours.…”