Location: Children's Nutrition Research CenterTitle: Stimulation of skeletal muscle protein synthesis in neonatal pigs by long-term infusion of leucine is amino acid dependent) Author
Submitted to: Journal of Animal Science
Publication Type: Abstract only
Publication Acceptance Date: 4/24/2009
Publication Date: 7/12/2009
Citation: Wilson, F.A., Suryawan, A., Gazzaneo, M.C., Orellana, R.A., Nguyen, H.V., Davis, T.A. 2009. Stimulation of skeletal muscle protein synthesis in neonatal pigs by long-term infusion of leucine is amino acid dependent [abstract]. The Joint Conference of the American Society of Animal Science and the American Dairy Science Association, Session: Growth and development: Physiology of growth in vivo and in vitro, July 12-16, 2009, Montreal, Quebec, Canada. 87(E-Suppl 2):321. Interpretive Summary:
Technical Abstract: Infusing leucine for 1 hr increases skeletal muscle protein synthesis in neonatal pigs, but this is not sustained for 2 h unless the leucine-induced fall in amino acids is prevented. We aimed to determine whether continuous leucine infusion can stimulate protein synthesis for a prolonged period when baseline amino acids are maintained and to identify signalling mechanisms involved. Overnight fasted 7-d-old pigs were infused for 24 h with saline, leucine (400 umol/kg(-1)/h(-1)), or leucine with replacement amino acids (n=6/group). Fractional protein synthesis and translation control mechanisms were examined in skeletal muscle. Amino acid replacement prevented the leucine-induced fall in plasma amino acids. Leucine stimulated muscle protein synthesis (P<0.05), but only when replacement amino acids were infused to maintain fasting levels. Leucine had no effect on phosphorylation of protein kinase B, AMP-activated protein kinase, tuberous sclerosis complex 2, signalling proteins upstream of mammalian target of rapamycin (mTOR). Leucine also did not alter phosphorylation of raptor or PRAS40 nor the association of mTOR with raptor, GbetaL, or rictor, regulators of mTOR. Phosphorylation of mTOR, as well as its downstream targets that regulate translation initiation, eukaryotic initiation factor (eIF)4E binding protein (4EBP1) and ribosomal protein S6 kinase, as well as eIF4E/eIF4G association were increased, and eIF2alpha phosphorylation was reduced by leucine, in the absence and presence of replacement amino acids (P<0.05). Thus, prolonged infusion of leucine activates mTOR and its downstream targets that regulate translation in skeletal muscle, irrespective of the circulating levels of the other amino acids. However, the ability of leucine to stimulate muscle protein synthesis is dependent upon amino acid availability.