Location: Children's Nutrition Research CenterTitle: Leucine acts as a nutrient signal to stimulate protein synthesis) Author
Submitted to: Journal of Animal Science
Publication Type: Abstract only
Publication Acceptance Date: 9/1/2010
Publication Date: 10/8/2010
Citation: Davis, T.A., Suryawan, A., Orellana, R.A., Fiorotto, M.L. 2010. Leucine acts as a nutrient signal to stimulate protein synthesis [abstract]. Journal of Animal Science. 88(E-Suppl. 2):2. Interpretive Summary:
Technical Abstract: The postprandial rise in amino acids and insulin independently stimulates protein synthesis in skeletal muscle of piglets. Leucine is an important mediator of the response to amino acids. We have shown that the postprandial rise in leucine, but not isoleucine or valine, acutely stimulates muscle protein synthesis in piglets. Leucine increases muscle protein synthesis by modulating the activation of signaling components of translation initiation. Thus, leucine increases the phosphorylation of mammalian target of rapamycin (mTOR), 70-kDa ribosomal protein S6 kinase, eukaryotic initiation factor (eIF)4E-binding protein-1, and eIF4G, decreases the phosphorylation of eIF2 a, and increases the association of eIF4E with eIF4G. However, leucine does not affect the canonical upstream activators of mTOR, i.e., protein kinase B, AMP-activated protein kinase, and tuberous sclerosis complex 1/2, or the translation elongation regulator, eukaryotic elongation factor 2. The acute leucine-induced stimulation of muscle protein synthesis is not maintained for prolonged periods, despite continued activation of the mTOR signaling pathway, because circulating essential amino acids fall as they are utilized as substrates for protein synthesis. However, if circulating amino acids levels are maintained, the leucine-induced stimulation of muscle protein synthesis can be maintained for prolonged periods. The activation of the mTOR signaling pathway by leucine does not appear to be affected by the circulating levels of other amino acids. Supplementation of low protein diets with leucine stimulates protein synthesis in muscle and most visceral tissues to a rate similar to that achieved by feeding high protein diets, and this stimulation involves activation of the mTOR downstream effectors. Together, these studies indicate that leucine acts as a nutrient signal to stimulate translation initiation but whether this translates into a sustained increase in protein synthesis.