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Intermittent Bolus Compared with Continuous Feeding Promotes Higher Activation of Insulin and Amino Acid Signaling to Protein Synthesis in Skeletal Muscle of Neonatal Pigs
Author(s) -
Suryawan Agus,
ElKadi Samer,
Nguyen Hanh,
Fiorotto Marta,
Davis Teresa
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.05154
Subject(s) - medicine , endocrinology , skeletal muscle , bolus (digestion) , insulin , protein kinase b , amino acid , meal , parenteral nutrition , chemistry , biology , phosphorylation , biochemistry
Previous studies in neonatal piglets demonstrated that nutritionally equivalent intakes administered as intermittent bolus feeds rather than continuously promoted greater protein synthesis rates in skeletal muscle and were associated with increased lean growth. However, the molecular mechanisms responsible for this response remain unclear. We aimed to identify the insulin and/or amino acid signaling pathway components involved in the enhanced stimulation of skeletal muscle protein synthesis by intermittent bolus compared to continuous feeding in neonatal pigs born at term. We hypothesized that compared to continuous feeding, intermittent bolus feeding would elicit greater activation of insulin and amino acid signaling components toward muscle protein synthesis in term pigs. In this study, piglets (2‐3 d old) were fed equal amounts {240 ml/(kg body weight [BW]/d)} of sow milk replacer {12.8 g protein and 155 kcal/(kg BW/d)} by orogastric tube either as intermittent bolus meals every 4 h (INT) or by continuous infusion (CON). After 21 d, gastrocnemius muscle was collected from CON, INT‐0 (before a meal), and INT‐60 (60 min after a meal) groups (n = 6/group). Fractional protein synthesis rate, body weight and composition, and abundance and phosphorylation of upstream and downstream insulin‐ and amino‐acid‐signaling components of relevance to mTORC1 activation and protein translation were measured. Body weight and gastrocnemius muscle mass and protein synthesis rate were greater in INT‐60 than in CON (P < 0.05). Phosphorylation of IR, IRS‐1, PDK1, mTORC2, pan‐Akt, Akt1, Akt2, and TSC2 were greater in INT‐60 than INT‐0 and CON (P < 0.05) but phosphorylation of PTEN, PP2A, Akt3, ERK 1/2, and AMPK, and abundance of PHLPP, SHIP‐2, and Ubl4A were similar. Association of Sestrin1 and 2 with GATOR2, but not CASTOR1 with GATOR2, were lower in INT‐60 than CON and INT‐0 (P < 0.05). Association of mTOR with RagA, RagC, and Rheb and phosphorylation of S6K1 and 4EBP1, but not eIF2alpha and eEF2, were higher in INT‐60 than INT‐0 and CON (P < 0.05). In conclusion, the enhanced rate of muscle protein synthesis and growth with intermittent bolus compared to continuous feeding can be explained by enhanced activation of both insulin and amino acid signaling pathways that regulate translation initiation.