PMID- 20505962 OWN - NLM STAT- MEDLINE DCOM- 20110420 LR - 20211020 IS - 1438-2199 (Electronic) IS - 0939-4451 (Print) IS - 0939-4451 (Linking) VI - 40 IP - 1 DP - 2011 Jan TI - Differential effects of long-term leucine infusion on tissue protein synthesis in neonatal pigs. PG - 157-65 LID - 10.1007/s00726-010-0629-9 [doi] AB - Leucine is unique among the amino acids in its ability to promote protein synthesis by activating translation initiation via the mammalian target of rapamycin (mTOR) pathway. Previously, we showed that leucine infusion acutely stimulates protein synthesis in fast-twitch glycolytic muscle of neonatal pigs but this response cannot be maintained unless the leucine-induced fall in amino acids is prevented. To determine whether leucine can stimulate protein synthesis in muscles of different fiber types and in visceral tissues of the neonate in the long-term if baseline amino acid concentrations are maintained, overnight fasted neonatal pigs were infused for 24 h with saline, leucine (400 micromol kg(-1) h(-1)), or leucine with replacement amino acids to prevent the leucine-induced hypoaminoacidemia. Changes in the fractional rate of protein synthesis and activation of mTOR, as determined by eukaryotic initiation factor 4E binding protein (4E-BP1) and S6 kinase 1 (S6K1) phosphorylation, in the gastrocnemius and masseter muscles, heart, liver, jejunum, kidney, and pancreas were measured. Leucine increased mTOR activation in the gastrocnemius and masseter muscles, liver, and pancreas, in both the absence and presence of amino acid replacement. However, protein synthesis in these tissues was increased only when amino acids were infused to maintain baseline levels. There were no changes in mTOR signaling or protein synthesis in the other tissues we examined. Thus, long-term infusion of leucine stimulates mTOR signaling in skeletal muscle and some visceral tissues but the leucine-induced stimulation of protein synthesis in these tissues requires sustained amino acid availability. FAU - Wilson, Fiona A AU - Wilson FA AD - Department of Pediatrics, Baylor College of Medicine, United States Department of Agriculture/Agriculture Research Service Children's Nutrition Research Center, Houston, TX, 77030, USA. FAU - Suryawan, Agus AU - Suryawan A FAU - Orellana, Renan A AU - Orellana RA FAU - Gazzaneo, Maria C AU - Gazzaneo MC FAU - Nguyen, Hanh V AU - Nguyen HV FAU - Davis, Teresa A AU - Davis TA LA - eng GR - K08 AR051563/AR/NIAMS NIH HHS/United States GR - R01 AR044474/AR/NIAMS NIH HHS/United States GR - R01 AR044474-16/AR/NIAMS NIH HHS/United States GR - R01 AR-44474/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20100527 PL - Austria TA - Amino Acids JT - Amino acids JID - 9200312 RN - 0 (Amino Acids) RN - 0 (Eukaryotic Initiation Factor-4E) RN - GMW67QNF9C (Leucine) SB - IM MH - Amino Acids/metabolism MH - Animals MH - Animals, Newborn MH - Eukaryotic Initiation Factor-4E/metabolism MH - Infusions, Intravenous MH - Kidney/drug effects/metabolism MH - Leucine/*administration & dosage MH - Liver/drug effects/metabolism MH - Muscle, Skeletal/drug effects/metabolism MH - Pancreas/drug effects/metabolism MH - Phosphorylation MH - Protein Biosynthesis/*drug effects MH - Random Allocation MH - Signal Transduction/drug effects MH - Swine/genetics/*metabolism MH - Time PMC - PMC3139360 MID - NIHMS306133 EDAT- 2010/05/28 06:00 MHDA- 2011/04/22 06:00 PMCR- 2012/01/01 CRDT- 2010/05/28 06:00 PHST- 2010/03/12 00:00 [received] PHST- 2010/05/11 00:00 [accepted] PHST- 2010/05/28 06:00 [entrez] PHST- 2010/05/28 06:00 [pubmed] PHST- 2011/04/22 06:00 [medline] PHST- 2012/01/01 00:00 [pmc-release] AID - 10.1007/s00726-010-0629-9 [doi] PST - ppublish SO - Amino Acids. 2011 Jan;40(1):157-65. doi: 10.1007/s00726-010-0629-9. Epub 2010 May 27.