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Prematurity blunts the insulin- and amino acid-induced stimulation of translation initiation and protein synthesis in skeletal muscle of neonatal pigs.
Rudar, Marko; Naberhuis, Jane K; Suryawan, Agus; Nguyen, Hanh V; Stoll, Barbara; Style, Candace C; Verla, Mariatu A; Olutoye, Oluyinka O; Burrin, Douglas G; Fiorotto, Marta L; Davis, Teresa A.
Afiliação
  • Rudar M; United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
  • Naberhuis JK; Department of Animal Sciences, Auburn University, Auburn, Alabama.
  • Suryawan A; United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
  • Nguyen HV; United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
  • Stoll B; United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
  • Style CC; United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
  • Verla MA; Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
  • Olutoye OO; Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
  • Burrin DG; Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
  • Fiorotto ML; United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
  • Davis TA; United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Am J Physiol Endocrinol Metab ; 320(3): E551-E565, 2021 03 01.
Article em En | MEDLINE | ID: mdl-33427053
ABSTRACT
Extrauterine growth restriction in premature infants is largely attributed to reduced lean mass accretion and is associated with long-term morbidities. Previously, we demonstrated that prematurity blunts the feeding-induced stimulation of translation initiation signaling and protein synthesis in skeletal muscle of neonatal pigs. The objective of the current study was to determine whether the blunted feeding response is mediated by reduced responsiveness to insulin, amino acids, or both. Pigs delivered by cesarean section preterm (PT; 103 days, n = 25) or at term (T; 112 days, n = 26) were subject to euinsulinemic-euaminoacidemic-euglycemic (FAST), hyperinsulinemic-euaminoacidemic-euglycemic (INS), or euinsulinemic-hyperaminoacidemic-euglycemic (AA) clamps four days after delivery. Indices of mechanistic target of rapamycin complex 1 (mTORC1) signaling and fractional protein synthesis rates were measured after 2 h. Although longissimus dorsi (LD) muscle protein synthesis increased in response to both INS and AA, the increase was 28% lower in PT than in T. Upstream of mTORC1, Akt phosphorylation, an index of insulin signaling, was increased with INS but was 40% less in PT than in T. The abundances of mTOR·RagA and mTOR·RagC, indices of amino acid signaling, increased with AA but were 25% less in PT than in T. Downstream of mTORC1, eIF4E·eIF4G abundance was increased by both INS and AA but attenuated by prematurity. These results suggest that preterm birth blunts both insulin- and amino acid-induced activation of mTORC1 and protein synthesis in skeletal muscle, thereby limiting the anabolic response to feeding. This anabolic resistance likely contributes to the high prevalence of extrauterine growth restriction in prematurity.NEW & NOTEWORTHY Extrauterine growth faltering is a major complication of premature birth, but the underlying cause is poorly understood. Our results demonstrate that preterm birth blunts both the insulin-and amino acid-induced activation of mTORC1-dependent translation initiation and protein synthesis in skeletal muscle, thereby limiting the anabolic response to feeding. This anabolic resistance likely contributes to the reduced accretion of lean mass and extrauterine growth restriction of premature infants.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Iniciação Traducional da Cadeia Peptídica / Biossíntese de Proteínas / Músculo Esquelético / Nascimento Prematuro / Aminoácidos / Insulina Tipo de estudo: Risk_factors_studies Limite: Animals / Pregnancy Idioma: En Revista: Am J Physiol Endocrinol Metab Assunto da revista: ENDOCRINOLOGIA / FISIOLOGIA / METABOLISMO Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Iniciação Traducional da Cadeia Peptídica / Biossíntese de Proteínas / Músculo Esquelético / Nascimento Prematuro / Aminoácidos / Insulina Tipo de estudo: Risk_factors_studies Limite: Animals / Pregnancy Idioma: En Revista: Am J Physiol Endocrinol Metab Assunto da revista: ENDOCRINOLOGIA / FISIOLOGIA / METABOLISMO Ano de publicação: 2021 Tipo de documento: Article