Journal
JOURNAL OF NUTRITION
Volume 151, Issue 9, Pages 2636-2645Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jn/nxab190
Keywords
neonate; insulin; amino acids; skeletal muscle; translation initiation
Categories
Funding
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR044474, AR46308]
- National Institute of Child Health and Human Development [HD072891, HD085573, HD099080]
- USDA National Institute of Agriculture [2013-67015-20438]
- USDA/Agricultural Research Service [3092-51000-060]
- NIFA [577883, 2013-67015-20438] Funding Source: Federal RePORTER
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In a neonatal piglet model, intermittent bolus feeding promotes greater protein synthesis rates in skeletal muscle compared to continuous feeding, potentially through enhanced insulin and amino acid signaling pathways.
Background: 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 eIF2 alpha 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.
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