Effect of branched-chain amino acid ratio on the proliferation, differentiation, and expression levels of key regulators involved in protein metabolism of myocytes
Yehui DuanNutrition Volume 36, April 2017, Pages 8–16
Highlights
• Optimal branched-chain amino acid (BCAA) ratio promoted myocytes proliferation and differentiation.
• Optimal BCAA ratio activated the nutrient sensor mTORC1 pathway of myocytes.
• The expression level of myogenic factors of myocytes was regulated by different BCAA ratios.
Branched-chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile), and valine (Val), are key regulators of protein synthesis in muscle. The aim of this study was to investigate the effect of different BCAA ratios (Leu:Ile:Val) on the proliferation, differentiation, and expression levels of the regulators related to protein metabolism of C2 C12 myocytes.
Methods
Studies were conducted in C2C12 myocytes exposed to different BCAA ratios (Leu: Ile: Val = 0, 1:0.25:0.25, 1:1:1).
Results
The ratio of 1:0.25:0.25 increased cell viability and promoted cell cycle progression from G0/G1 phase to S phase, which was an indicator of proliferation enhancement (P < 0.05). Moreover, this optimal ratio (1:0.25:0.25) promoted the differentiation of myocytes into myotubes by upregulating myogenin and interleukin-15 gene expression, and differently regulated the expression of L-type amino acid transporter 1 and 4 and system ASC amino acid transporters 2. Furthermore, the ratio stimulated mTOR expression at the mRNA and phosphorylated protein levels, as well as ribosomal protein S6 kinase and regulatory-associated protein of mTOR (raptor). In contrast, the optimal ratio decreased the amount of ubiquitin ligase muscle-specific RING finger 1 and muscle atrophy F-box during proliferation and differentiatio[n/b] (P < 0.05). No change was observed in the expression of key genes related to energy metabolism except for uncoupling protein 3 (P > 0.05).
Conclusions
The results suggested that appropriate [b]BCAA ratios could enhance proliferation and differentiation of the C2 C12 myocytes, also mediate the key regulators related to protein metabolism including the mTORC1 pathway. A proper utilization of balanced BCAA ratio in food would be beneficial to human and animal nutrition.