|Suryawan, Agus -|
|Orellana, Renan -|
|Fiorotto, Marta -|
|Davis, Teresa -|
Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 2, 2010
Publication Date: October 8, 2010
Citation: Suryawan, A., Orellana, R.A., Fiorotto, M.L., Davis, T.A. 2010. Triennial growth symposium: Leucine acts as a nutrient signal to stimulate protein synthesis in neonatal pigs. Journal of Animal Science. 89(7):2004-2016. Interpretive Summary: This paper summarizes the role of leucine as an important mediator of the effect of amino acids on protein synthesis. The molecular mechanism by which leucine acts has been found using cell cultures. We found that leucine stimulates protein synthesis through the activation of the mammalian target of rapamycin complex 1 (mTORC1) and signaling components that act directly to protein synthesis process. Leucine seems to act through a different pathway than insulin. In summary, leucine acts as nutrient signal to stimulate protein synthesis. Information regarding leucine can be useful for formulating strategies to increase the growth of human neonates.
Technical Abstract: The postprandial increases in AA and insulin independently stimulate protein synthesis in skeletal muscle of piglets. Leucine is an important mediator of the response to AA. We have shown that the postprandial increase in leucine, but not isoleucine or valine, acutely stimulates muscle protein synthesis in piglets. Leucine increases muscle protein synthesis by modulating the activation of mammalian target of rapamycin (mTOR) complex 1 and signaling components of translation initiation. Leucine increases the phosphorylation of mTOR, 70-kDa ribosomal protein S6 kinase-1, eukaryotic initiation factor (eIF) 4E-binding protein-1, and eIF4G; decreases eIF2alpha phosphorylation; and increases the association of eIF4E with eIF4G. However, leucine does not affect the upstream activators of mTOR, that is, protein kinase B, adenosine monophosphate-activated protein kinase, and tuberous sclerosis complex 1/2, or the activation of translation elongation regulator, eukaryotic elongation factor 2. The action of leucine can be replicated by alpha-ketoisocaproate but not by norleucine. Interference by rapamycin with the raptor-mTOR interaction blocks leucine-induced muscle protein synthesis. The acute leucine-induced stimulation of muscle protein synthesis is not maintained for prolonged periods, despite continued activation of mTOR signaling, because circulating AA fall as they are utilized for protein synthesis. However, when circulating AA concentrations are maintained, the leucine-induced stimulation of muscle protein synthesis is maintained for prolonged periods. Thus, leucine acts as a nutrient signal to stimulate translation initiation, but whether this translates into a prolonged increase in protein synthesis depends on the sustained availability of all AA.