Regulation of skeletal muscle protein synthesis in the preterm pig by intermittent leucine pulses during continuous parenteral feeding.
Infant, Newborn
Female
Humans
Animals
Swine
Leucine
/ metabolism
Animals, Newborn
Premature Birth
/ metabolism
Muscle, Skeletal
/ metabolism
TOR Serine-Threonine Kinases
Mechanistic Target of Rapamycin Complex 1
/ metabolism
Alanine
/ metabolism
Muscle Proteins
/ metabolism
Parenteral Nutrition
Protein Biosynthesis
mTOR
parenteral nutrition
pig
prematurity
protein synthesis
skeletal muscle
Journal
JPEN. Journal of parenteral and enteral nutrition
ISSN: 1941-2444
Titre abrégé: JPEN J Parenter Enteral Nutr
Pays: United States
ID NLM: 7804134
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
31
08
2022
received:
30
06
2022
accepted:
15
09
2022
pmc-release:
01
02
2024
pubmed:
22
9
2022
medline:
10
2
2023
entrez:
21
9
2022
Statut:
ppublish
Résumé
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. 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 µmol kg 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. Intermittent pulses of Leu do not enhance muscle protein anabolism in preterm pigs supplied continuous parenteral nutrition.
Sections du résumé
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 µmol kg
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.
Identifiants
pubmed: 36128996
doi: 10.1002/jpen.2450
pmc: PMC10621874
mid: NIHMS1940859
doi:
Substances chimiques
Leucine
GMW67QNF9C
TOR Serine-Threonine Kinases
EC 2.7.11.1
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Alanine
OF5P57N2ZX
Muscle Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
276-286Subventions
Organisme : NICHD NIH HHS
ID : R01 HD099080
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD072891
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD085573
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR044474
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32DK007664
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007664
Pays : United States
Informations de copyright
© 2022 American Society for Parenteral and Enteral Nutrition.
Références
Natl Vital Stat Rep. 2021 Feb;70(17):1-50
pubmed: 35157571
Science. 2011 Nov 4;334(6056):678-83
pubmed: 22053050
J Biol Chem. 2020 Mar 6;295(10):2890-2899
pubmed: 32019866
J Anim Sci. 2013 Oct;91(10):4713-29
pubmed: 23942716
Pediatrics. 2006 Apr;117(4):1253-61
pubmed: 16585322
Am J Physiol Endocrinol Metab. 2016 Apr 15;310(8):E699-E713
pubmed: 26884386
Pediatrics. 2010 Sep;126(3):443-56
pubmed: 20732945
Curr Opin Pediatr. 1997 Jun;9(3):270-5
pubmed: 9229168
Clin Perinatol. 2017 Jun;44(2):395-406
pubmed: 28477668
Pediatr Res. 2007 Sep;62(3):353-6
pubmed: 17622957
Clin Liver Dis. 1998 Feb;2(1):1-30, v
pubmed: 15560043
J Physiol. 2013 Jun 1;591(11):2911-23
pubmed: 23551944
Am J Physiol Endocrinol Metab. 2021 Dec 1;321(6):E737-E752
pubmed: 34719946
Science. 2013 May 31;340(6136):1100-6
pubmed: 23723238
J Biol Chem. 2010 Oct 29;285(44):33718-26
pubmed: 20736162
J Nutr. 2011 Dec;141(12):2152-8
pubmed: 22013195
Nat Rev Endocrinol. 2017 Jan;13(1):50-62
pubmed: 27539244
J Nutr. 2010 Aug;140(8):1418-24
pubmed: 20534881
Curr Opin Clin Nutr Metab Care. 2009 Jan;12(1):78-85
pubmed: 19057192
Am J Physiol Endocrinol Metab. 2005 May;288(5):E914-21
pubmed: 15644455
Pediatrics. 2015 Jul;136(1):e84-92
pubmed: 26101360
Science. 2015 Jan 9;347(6218):188-94
pubmed: 25567906
Nutr Clin Pract. 2020 Feb;35(1):63-71
pubmed: 31872510
J Nutr. 2006 Jan;136(1 Suppl):232S-3S
pubmed: 16365088
Am J Physiol Endocrinol Metab. 2019 Nov 1;317(5):E839-E851
pubmed: 31503514
Neonatology. 2008;94(4):245-54
pubmed: 18836284
Am J Physiol Endocrinol Metab. 2013 Sep 1;305(5):E620-31
pubmed: 23839523
Am J Physiol Endocrinol Metab. 2003 Jan;284(1):E110-9
pubmed: 12388131
J Nutr. 1998 Mar;128(3):606-14
pubmed: 9482771
J Pediatr. 2019 Jul;210:69-80.e5
pubmed: 30992219
Cell Rep. 2014 Oct 9;9(1):1-8
pubmed: 25263562
Science. 2017 Nov 10;358(6364):813-818
pubmed: 29123071
Annu Rev Anim Biosci. 2020 Feb 15;8:321-354
pubmed: 32069436
Biochem Soc Trans. 2013 Aug;41(4):951-5
pubmed: 23863162
Annu Rev Anim Biosci. 2014 Feb;2:419-44
pubmed: 25384150
JPEN J Parenter Enteral Nutr. 2012 Sep;36(5):538-50
pubmed: 22549765
Am J Physiol Endocrinol Metab. 2021 Mar 1;320(3):E551-E565
pubmed: 33427053
Pediatrics. 2012 Sep;130(3):e640-9
pubmed: 22891222
J Perinatol. 2016 Jul;36(7):500-2
pubmed: 27339826
J Cell Sci. 2019 Nov 13;132(21):
pubmed: 31722960
Cell. 2016 Mar 24;165(1):153-164
pubmed: 26972053
Nature. 2021 Aug;596(7871):281-284
pubmed: 34290409
Am J Physiol Endocrinol Metab. 2012 Mar 15;302(6):E674-86
pubmed: 22215651
Science. 2016 Jan 1;351(6268):43-8
pubmed: 26449471