Leucine supplementation to improve the efficiency of utilization of dietary protein for lean growth

Abstract Text: Most premature infants experience extrauterine growth restriction by hospital discharge and many remain small to adulthood.  Similarly, early weaning of piglets may reduce food intake resulting in growth faltering.  Thus, strategies are needed to improve the efficiency of utilization of dietary amino acids for lean growth in early life.  Studies in the neonatal pig model have shown that the sharp increase in muscle protein synthesis after eating is mediated by the rise in amino acids and insulin.  Amino acids and insulin induce protein synthesis by activating independent signaling pathways that converge at mechanistic target of rapamycin complex 1 (mTORC1), leading to the activation of key regulators of translation.  Leucine is the most effective single amino acid in triggering translation initiation factor activation.  Acute parenteral leucine administration at physiological levels increases muscle protein synthesis in neonatal pigs and this effect is due to the activation of mTORC1 and its downstream targets, including eukaryotic initiation factor 4E-binding protein 1 and ribosomal protein S6 kinase-1.  Although acute administration of the other branched-chain amino acids, isoleucine and valine, is less effective, the leucine metabolites, α-ketoisocaproic acid and β-hydroxy-β-methylbutyrate, stimulate muscle protein synthesis by activating mTORC1-dependent translation to the same extent as leucine.  The stimulation of protein synthesis by parenteral leucine can be sustained for prolonged periods, but requires the maintenance of the supply of other amino acids to support protein synthesis.  Pulsatile administration of leucine during continuous orogastric feeding of a milk replacer enhances muscle protein synthesis by stimulating translation initiation.  Enteral leucine supplementation of a low protein meal stimulates protein synthesis to the same extent as a high protein meal but this effect diminishes with more prolonged supplementation.  Whether the anabolic effects of leucine can be sustained chronically to promote lean growth requires further study.  (Supported by NIH AR444474, NIH HD072891, USDA NIFA 2013-67015-20438, and USDA/ARS 6250-51000-055)

Keywords: Amino acids, muscle, growth