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Intermittent Bolus Compared with Continuous Feeding Enhances Insulin and Amino Acid Signaling to Translation Initiation in Skeletal Muscle of Neonatal Pigs

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dc.contributor.authorSuryawan, Agusen
dc.contributor.authorEl-Kadi, Samer Wassimen
dc.contributor.authorNguyen, Hanh V.en
dc.contributor.authorFiorotto, Marta L.en
dc.contributor.authorDavis, Teresa A.en
dc.date.accessioned2022-01-07T15:30:08Zen
dc.date.available2022-01-07T15:30:08Zen
dc.date.issued2021-09-01en
dc.date.updated2022-01-07T15:30:06Zen
dc.description.abstractBackground: Nutrition administered as intermittent bolus feeds rather than continuously promotes greater protein synthesis rates in skeletal muscle and enhances lean growth in a neonatal piglet model. The molecular mechanisms responsible remain unclear. Objectives: We aimed to identify the insulin- and/or amino acid-signaling components involved in the enhanced stimulation of skeletal muscle by intermittent bolus compared to continuous feeding in neonatal pigs born at term. Methods: Term piglets (2-3 days old) were fed equal amounts of sow milk replacer [12.8 g protein and 155 kcal/(kg body weight · d)] by orogastric tube as intermittent bolus meals every 4 hours (INT) or by continuous infusion (CTS). After 21 days, gastrocnemius muscle samples were collected from CTS, INT-0 (before a meal), and INT-60 (60 minutes after a meal) groups (n = 6/group). Insulin- and amino acid-signaling components relevant to mechanistic target of rapamycin complex (mTORC) 1 activation and protein translation were measured. Results: Phosphorylation of the insulin receptor, IRS-1, PDK1, mTORC2, pan-Akt, Akt1, Akt2, and TSC2 was 106% to 273% higher in the skeletal muscle of INT-60 piglets than in INT-0 and CTS piglets (P < 0.05), but phosphorylation of PTEN, PP2A, Akt3, ERK1/2, and AMPK did not differ among groups, nor did abundances of PHLPP, SHIP2, and Ubl4A. The association of GATOR2 with Sestrin1/2, but not CASTOR1, was 51% to 52% lower in INT-60 piglets than in INT-0 and CTS piglets (P < 0.05), but the abundances of SLC7A5/LAT1, SLC38A2/SNAT2, SLC38A9, Lamtor1/2, and V-ATPase did not differ. Associations of mTOR with RagA, RagC, and Rheb and phosphorylation of S6K1 and 4EBP1, but not eIF2α and eEF2, were 101% to 176% higher in INT-60 piglets than in INT-0 and CTS piglets (P < 0.05). Conclusions: The enhanced rates of muscle protein synthesis and growth with intermittent bolus compared to continuous feeding in a neonatal piglet model can be explained by enhanced activation of both the insulin- and amino acid-signaling pathways that regulate translation initiation.en
dc.description.versionPublished versionen
dc.format.extentPages 2636-2645en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1093/jn/nxab190en
dc.identifier.eissn1541-6100en
dc.identifier.issn0022-3166en
dc.identifier.issue9en
dc.identifier.orcidEl-Kadi, Samer [0000-0001-5368-853X]en
dc.identifier.other6308086 (PII)en
dc.identifier.pmid34159368en
dc.identifier.urihttp://hdl.handle.net/10919/107450en
dc.identifier.volume151en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/34159368en
dc.rightsPublic Domainen
dc.rights.urihttp://creativecommons.org/publicdomain/mark/1.0/en
dc.subjectamino acidsen
dc.subjectinsulinen
dc.subjectneonateen
dc.subjectskeletal muscleen
dc.subjecttranslation initiationen
dc.subject0702 Animal Productionen
dc.subject0908 Food Sciencesen
dc.subject1111 Nutrition and Dieteticsen
dc.subjectNutrition & Dieteticsen
dc.titleIntermittent Bolus Compared with Continuous Feeding Enhances Insulin and Amino Acid Signaling to Translation Initiation in Skeletal Muscle of Neonatal Pigsen
dc.title.serialJournal of Nutritionen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
dcterms.dateAccepted2021-05-18en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Animal and Poultry Sciencesen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen

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