Preterm birth alters the feeding-induced activation of Akt signaling in the muscle of neonatal piglets.
Infant, Newborn
Pregnancy
Humans
Animals
Swine
Female
Proto-Oncogene Proteins c-akt
/ metabolism
TOR Serine-Threonine Kinases
/ metabolism
Premature Birth
/ metabolism
Cesarean Section
Animals, Newborn
Infant, Premature
Muscle, Skeletal
/ metabolism
Phosphotransferases (Phosphate Group Acceptor)
/ metabolism
Ubiquitins
/ metabolism
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
10
07
2022
accepted:
27
10
2022
revised:
04
10
2022
medline:
3
7
2023
pubmed:
20
11
2022
entrez:
19
11
2022
Statut:
ppublish
Résumé
Postnatal lean mass accretion is commonly reduced in preterm infants. This study investigated mechanisms involved in the blunted feeding-induced activation of Akt in the skeletal muscle of preterm pigs that contributes to lower protein synthesis rates. On day 3 following cesarean section, preterm and term piglets were fasted or fed an enteral meal. Activation of Akt signaling pathways in skeletal muscle was determined. Akt1 and Akt2, but not Akt3, phosphorylation were lower in the skeletal muscle of preterm than in term pigs (P < 0.05). Activation of Akt-positive regulators, PDK1 and mTORC2, but not FAK, were lower in preterm than in term (P < 0.05). The formation of Akt complexes with GAPDH and Hsp90 and the abundance of Ubl4A were lower in preterm than in term (P < 0.05). The abundance of Akt inhibitors, PHLPP and SHIP2, but not PTEN and IP6K1, were higher in preterm than in term pigs (P < 0.05). PP2A activation was inhibited by feeding in term but not in preterm pigs (P < 0.05). Our results suggest that preterm birth impairs regulatory components involved in Akt activation, thereby limiting the anabolic response to feeding. This anabolic resistance likely contributes to the reduced lean accretion following preterm birth. The Akt-mTORC1 pathway plays an important role in the regulation of skeletal muscle protein synthesis in neonates. This is the first evidence to demonstrate that, following preterm birth, the postprandial activation of positive regulators of Akt in the skeletal muscle is reduced, whereas the activation of negative regulators of Akt is enhanced. This anabolic resistance of Akt signaling in response to feeding likely contributes to the reduced accretion of lean mass in premature infants. These results may provide potential novel molecular targets for intervention to enhance lean growth in preterm neonates.
Sections du résumé
BACKGROUND
BACKGROUND
Postnatal lean mass accretion is commonly reduced in preterm infants. This study investigated mechanisms involved in the blunted feeding-induced activation of Akt in the skeletal muscle of preterm pigs that contributes to lower protein synthesis rates.
METHODS
METHODS
On day 3 following cesarean section, preterm and term piglets were fasted or fed an enteral meal. Activation of Akt signaling pathways in skeletal muscle was determined.
RESULTS
RESULTS
Akt1 and Akt2, but not Akt3, phosphorylation were lower in the skeletal muscle of preterm than in term pigs (P < 0.05). Activation of Akt-positive regulators, PDK1 and mTORC2, but not FAK, were lower in preterm than in term (P < 0.05). The formation of Akt complexes with GAPDH and Hsp90 and the abundance of Ubl4A were lower in preterm than in term (P < 0.05). The abundance of Akt inhibitors, PHLPP and SHIP2, but not PTEN and IP6K1, were higher in preterm than in term pigs (P < 0.05). PP2A activation was inhibited by feeding in term but not in preterm pigs (P < 0.05).
CONCLUSIONS
CONCLUSIONS
Our results suggest that preterm birth impairs regulatory components involved in Akt activation, thereby limiting the anabolic response to feeding. This anabolic resistance likely contributes to the reduced lean accretion following preterm birth.
IMPACT
CONCLUSIONS
The Akt-mTORC1 pathway plays an important role in the regulation of skeletal muscle protein synthesis in neonates. This is the first evidence to demonstrate that, following preterm birth, the postprandial activation of positive regulators of Akt in the skeletal muscle is reduced, whereas the activation of negative regulators of Akt is enhanced. This anabolic resistance of Akt signaling in response to feeding likely contributes to the reduced accretion of lean mass in premature infants. These results may provide potential novel molecular targets for intervention to enhance lean growth in preterm neonates.
Identifiants
pubmed: 36402914
doi: 10.1038/s41390-022-02382-4
pii: 10.1038/s41390-022-02382-4
pmc: PMC10195917
mid: NIHMS1847230
doi:
Substances chimiques
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
IP6K1 protein, human
EC 2.7.4.21
Phosphotransferases (Phosphate Group Acceptor)
EC 2.7.4.-
Ubl4A protein, human
0
Ubiquitins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1891-1898Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR044474
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD072891
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD085573
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD099080
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
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