PMID- 36128996 OWN - NLM STAT- MEDLINE DCOM- 20230209 LR - 20240202 IS - 1941-2444 (Electronic) IS - 0148-6071 (Print) IS - 0148-6071 (Linking) VI - 47 IP - 2 DP - 2023 Feb TI - Regulation of skeletal muscle protein synthesis in the preterm pig by intermittent leucine pulses during continuous parenteral feeding. PG - 276-286 LID - 10.1002/jpen.2450 [doi] AB - BACKGROUND: Extrauterine growth restriction is a common complication of preterm birth. Leucine (Leu) is an agonist for the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway that regulates translation initiation and protein synthesis in skeletal muscle. Previously, we showed that intermittent intravenous pulses of Leu to neonatal pigs born at term receiving continuous enteral nutrition increases muscle protein synthesis and lean mass accretion. Our objective was to determine the impact of intermittent intravenous pulses of Leu on muscle protein anabolism in preterm neonatal pigs administered continuous parenteral nutrition. METHODS: Following preterm delivery (on day 105 of 115 gestation), pigs were fitted with umbilical artery and jugular vein catheters and provided continuous parenteral nutrition. Four days after birth, pigs were assigned to receive intermittent Leu (1600 micromol kg(-1) h(-1) ; n = 8) or alanine (1600 micromol kg(-1) h(-1) ; n = 8) parenteral pulses every 4 h for 28 h. Anabolic signaling and fractional protein synthesis were determined in skeletal muscle. RESULTS: Leu concentration in the longissimus dorsi and gastrocnemius muscles increased in the leucine (LEU) group compared with the alanine (ALA) group (P < 0.0001). Despite the Leu-induced disruption of the Sestrin2.GATOR2 complex, which inhibits mTORC1 activation, in these muscles (P < 0.01), the abundance of mTOR.RagA and mTOR.RagC was not different. Accordingly, mTORC1-dependent activation of 4EBP1, S6K1, eIF4E.eIF4G, and protein synthesis were not different in any muscle between the LEU and ALA groups. CONCLUSION: Intermittent pulses of Leu do not enhance muscle protein anabolism in preterm pigs supplied continuous parenteral nutrition. CI - (c) 2022 American Society for Parenteral and Enteral Nutrition. FAU - Rudar, Marko AU - Rudar M AD - Department of Animal Sciences, Auburn University, Auburn, Alabama, USA. FAU - Suryawan, Agus AU - Suryawan A AD - USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA. FAU - Nguyen, Hanh V AU - Nguyen HV AD - USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA. FAU - Chacko, Shaji K AU - Chacko SK AD - USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA. FAU - Vonderohe, Caitlin AU - Vonderohe C AD - USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA. FAU - Stoll, Barbara AU - Stoll B AD - USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA. FAU - Burrin, Douglas G AU - Burrin DG AUID- ORCID: 0000-0002-8792-3339 AD - USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA. FAU - Fiorotto, Marta L AU - Fiorotto ML AD - USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA. FAU - Davis, Teresa A AU - Davis TA AUID- ORCID: 0000-0002-4610-9795 AD - USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA. LA - eng GR - R01 HD099080/HD/NICHD NIH HHS/United States GR - R01 HD072891/HD/NICHD NIH HHS/United States GR - R01 HD085573/HD/NICHD NIH HHS/United States GR - R01 AR044474/AR/NIAMS NIH HHS/United States GR - T32DK007664/DK/NIDDK NIH HHS/United States GR - T32 DK007664/DK/NIDDK 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 - 20221010 PL - United States TA - JPEN J Parenter Enteral Nutr JT - JPEN. Journal of parenteral and enteral nutrition JID - 7804134 RN - GMW67QNF9C (Leucine) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - OF5P57N2ZX (Alanine) RN - 0 (Muscle Proteins) SB - IM MH - Infant, Newborn MH - Female MH - Humans MH - Animals MH - Swine MH - Leucine/metabolism/pharmacology MH - Animals, Newborn MH - *Premature Birth/metabolism MH - Muscle, Skeletal/metabolism MH - TOR Serine-Threonine Kinases MH - Mechanistic Target of Rapamycin Complex 1/metabolism MH - Alanine/metabolism MH - Muscle Proteins/metabolism MH - Parenteral Nutrition MH - Protein Biosynthesis PMC - PMC10621874 MID - NIHMS1940859 OTO - NOTNLM OT - mTOR OT - parenteral nutrition OT - pig OT - prematurity OT - protein synthesis OT - skeletal muscle COIS- CONFLICT OF INTEREST None declared. EDAT- 2022/09/22 06:00 MHDA- 2023/02/10 06:00 PMCR- 2024/02/01 CRDT- 2022/09/21 06:13 PHST- 2022/08/31 00:00 [revised] PHST- 2022/06/30 00:00 [received] PHST- 2022/09/15 00:00 [accepted] PHST- 2022/09/22 06:00 [pubmed] PHST- 2023/02/10 06:00 [medline] PHST- 2022/09/21 06:13 [entrez] PHST- 2024/02/01 00:00 [pmc-release] AID - 10.1002/jpen.2450 [doi] PST - ppublish SO - JPEN J Parenter Enteral Nutr. 2023 Feb;47(2):276-286. doi: 10.1002/jpen.2450. Epub 2022 Oct 10.