scholarly journals Anabolic signaling and protein deposition are enhanced by intermittent compared with continuous feeding in skeletal muscle of neonates

2012 ◽  
Vol 302 (6) ◽  
pp. E674-E686 ◽  
Author(s):  
Samer W. El-Kadi ◽  
Agus Suryawan ◽  
Maria C. Gazzaneo ◽  
Neeraj Srivastava ◽  
Renán A. Orellana ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Whole Body ◽  
Signaling Proteins ◽  
Protein Deposition ◽  
Intermittent Bolus ◽  
Continuous Feeding

Orogastric tube feeding is indicated for neonates with impaired ability to ingest and can be administered by intermittent bolus or continuous schedule. Our aim was to determine whether feeding modalities affect muscle protein deposition and to identify mechanisms involved. Neonatal pigs were overnight fasted (FAS) or fed the same amount of food continuously (CON) or intermittently (INT; 7 × 4 h meals) for 29 h. For 8 h, between hours 20 and 28, pigs were infused with [2H5]phenylalanine and [2H2]tyrosine, and amino acid (AA) net balances were measured across the hindquarters. Insulin, branched-chain AA, phenylalanine, and tyrosine arterial concentrations and whole body phenylalanine and tyrosine fluxes were greater for INT after the meal than for CON or FAS. The activation of signaling proteins leading to initiation of mRNA translation, including eukaryotic initiation factor (eIF)4E·eIF4G complex formation in muscle, was enhanced by INT compared with CON feeding or FAS. Signaling proteins of protein degradation were not affected by feeding modalities except for microtubule-associated protein light chain 3-II, which was highest in the FAS. Across the hindquarters, AA net removal increased for INT but not for CON or FAS, with protein deposition greater for INT. This was because protein synthesis increased following feeding for INT but remained unchanged for CON and FAS, whereas there was no change in protein degradation across any dietary treatment. These results suggest that muscle protein accretion in neonates is enhanced with intermittent bolus to a greater extent than continuous feeding, mainly by increased protein synthesis.

scholarly journals Intermittent Bolus Feeding Enhances Organ Growth More Than Continuous Feeding in a Neonatal Piglet Model

2020 ◽  
Vol 4 (12) ◽  
Author(s):  
Samer W El-Kadi ◽  
Claire Boutry-Regard ◽  
Agus Suryawan ◽  
Hanh V Nguyen ◽  
Scot R Kimball ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Weight Gain ◽  
Translation Initiation ◽  
Initiation Factor ◽  
Whole Body ◽  
Feeding Frequency ◽  
Organ Growth ◽  
Intermittent Feeding ◽  
Intermittent Bolus ◽  
Continuous Feeding

ABSTRACT Background Orogastric tube feeding is frequently prescribed for neonates who cannot ingest food normally. In a piglet model of the neonate, greater skeletal muscle growth is sustained by upregulation of translation initiation signaling when nutrition is delivered by intermittent bolus meals, rather than continuously. Objectives The objective of this study was to determine the long-term effects of feeding frequency on organ growth and the mechanism by which feeding frequency modulates protein anabolism in these organs. Methods Eighteen neonatal pigs were fed by gastrostomy tube the same amount of a sow milk replacer either by continuous infusion (CON) or on an intermittent bolus schedule (INT). After 21 d of feeding, the pigs were killed without interruption of feeding (CON; n = 6) or immediately before (INT-0; n = 6) or 60 min after (INT-60; n = 6) a meal, and fractional protein synthesis rates and activation indexes of signaling pathways that regulate translation initiation were measured in the heart, jejunum, ileum, kidneys, and liver. Results Compared with continuous feeding, intermittent feeding stimulated the growth of the liver (+64%), jejunum (+48%), ileum (+40%), heart (+64%), and kidney (+56%). The increases in heart, kidney, jejunum, and ileum masses were proportional to whole body lean weight gain, but liver weight gain was greater in the INT-60 than the CON, and intermediate for the INT-0 group. For the liver and ileum, but not the heart, kidney, and jejunum, INT-60 compared with CON pigs had greater fractional protein synthesis rates (22% and 48%, respectively) and was accompanied by an increase in ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E binding protein 1 phosphorylation. Conclusions These results suggest that intermittent bolus compared with continuous orogastric feeding enhances organ growth and that in the ileum and liver, intermittent feeding enhances protein synthesis by stimulating translation initiation.

Physiological rise in plasma leucine stimulates muscle protein synthesis in neonatal pigs by enhancing translation initiation factor activation

2005 ◽  
Vol 288 (5) ◽  
pp. E914-E921 ◽  
Author(s):  
Jeffery Escobar ◽  
Jason W. Frank ◽  
Agus Suryawan ◽  
Hanh V. Nguyen ◽  
Scot R. Kimball ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Neonatal Pigs ◽  
Plasma Leucine

Protein synthesis in skeletal muscle of adult rats increases in response to oral gavage of supraphysiological doses of leucine. However, the effect on protein synthesis of a physiological rise in plasma leucine has not been investigated in neonates, an anabolic population highly sensitive to amino acids and insulin. Therefore, in the current study, fasted pigs were infused intra-arterially with leucine (0, 200, or 400 μmol·kg−1·h−1), and protein synthesis was measured after 60 or 120 min. Protein synthesis was increased in muscle, but not in liver, at 60 min. At 120 min, however, protein synthesis returned to baseline levels in muscle but was reduced below baseline values in liver. The increase in protein synthesis in muscle was associated with increased plasma leucine of 1.5- to 3-fold and no change in plasma insulin. Leucine infusion for 120 min reduced plasma essential amino acid levels. Phosphorylation of eukaryotic initiation factor (eIF)-4E-binding protein-1 (4E-BP1), ribosomal protein (rp) S6 kinase, and rpS6 was increased, and the amount of eIF4E associated with its repressor 4E-BP1 was reduced after 60 and 120 min of leucine infusion. No change in these biomarkers of mRNA translation was observed in liver. Thus a physiological increase in plasma leucine stimulates protein synthesis in skeletal muscle of neonatal pigs in association with increased eIF4E availability for eIF4F assembly. This response appears to be insulin independent, substrate dependent, and tissue specific. The results suggest that the branched-chain amino acid leucine can act as a nutrient signal to stimulate protein synthesis in skeletal muscle of neonates.

Skeletal muscle eEF2 and 4EBP1 phosphorylation during endurance exercise is dependent on intensity and muscle fiber type

2009 ◽  
Vol 296 (2) ◽  
pp. R326-R333 ◽  
Author(s):  
Adam J. Rose ◽  
Bruno Bisiani ◽  
Bodil Vistisen ◽  
Bente Kiens ◽  
Erik A. Richter
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Exercise Intensity ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Fiber Type ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Type I ◽  
Α Subunit

Protein synthesis in skeletal muscle is known to decrease during exercise, and it has been suggested that this may depend on the magnitude of the relative metabolic stress within the contracting muscle. To examine the mechanisms behind this, the effect of exercise intensity on skeletal muscle eukaryotic elongation factor 2 (eEF2) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) phosphorylation, key components in the mRNA translation machinery, were examined together with AMP-activated protein kinase (AMPK) in healthy young men. Skeletal muscle eEF2 phosphorylation at Thr56 increased during exercise but was not influenced by exercise intensity, and was lower than rest 30 min after exercise. On the other hand, 4EBP1 phosphorylation at Thr37/46 decreased during exercise, and this decrease was greater at higher exercise intensities and was similar to rest 30 min after exercise. AMPK activity, as indexed by AMPK α-subunit phosphorylation at Thr172 and phosphorylation of the AMPK substrate ACCβ at Ser221, was higher with higher exercise intensities, and these indices were higher than rest after high-intensity exercise only. Using immunohistochemistry, it was shown that the increase in skeletal muscle eEF2 Thr56 phosphorylation was restricted to type I myofibers. Taken together, these data suggest that the depression of skeletal muscle protein synthesis with endurance-type exercise may be regulated at both initiation (i.e., 4EBP1) and elongation (i.e., eEF2) steps, with eEF2 phosphorylation contributing at all exercise intensities but 4EBP1 dephosphorylation contributing to a greater extent at high vs. low exercise intensities.

scholarly journals Intermittent bolus feeding promotes greater lean growth than continuous feeding in a neonatal piglet model

2018 ◽  
Vol 108 (4) ◽  
pp. 830-841 ◽  
Author(s):  
Samer W El-Kadi ◽  
Claire Boutry ◽  
Agus Suryawan ◽  
Maria C Gazzaneo ◽  
Renán A Orellana ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Mass ◽  
Initiation Factor ◽  
Feeding Frequency ◽  
Orogastric Tube ◽  
Intermittent Bolus ◽  
Lean Growth ◽  
Continuous Feeding

Abstract Background Orogastric tube feeding is indicated in neonates with an impaired ability to ingest food normally and can be administered with an intermittent bolus or continuous feeding schedule. Objectives The objectives were to 1) compare the long-term effect of continuous with intermittent feeding on growth using the newborn pig as a model, 2) determine whether feeding frequency alters lean tissue and fat mass gain, and 3) identify the signaling mechanisms by which protein deposition is controlled in skeletal muscle in response to feeding frequency. Design Neonatal pigs were fed the same amount of a balanced formula by orogastric tube either as an intermittent bolus meal every 4 h (INT) or as a continuous infusion (CON). Body composition was assessed at the start and end of the study by dual-energy X-ray absorptiometry, and hormone and substrate profiles, muscle mass, protein synthesis, and indexes of nutrient and insulin signaling were measured after 21 d. Results Body weight, lean mass, spine length, and skeletal muscle mass were greater in the INT group than in the CON group. Skeletal muscle fractional protein synthesis rates were greater in the INT group after a meal than in the CON group and were associated with higher circulating branched-chain amino acid and insulin concentrations. Skeletal muscle protein kinase B (PKB) and ribosomal protein S6 kinase phosphorylation and eukaryotic initiation factor (eIF) 4E–eIF4G complex formation were higher, whereas eIF2α phosphorylation was lower in the INT group than in the CON group, indicating enhanced activation of insulin and amino acid signaling to translation initiation. Conclusions These results suggest that when neonates are fed the same amounts of nutrients as intermittent meals rather than continuously there is greater lean growth. This response can be ascribed, in part, to the pulsatile pattern of amino acids, insulin, or both induced by INT, which enables the responsiveness of anabolic pathways to feeding to be sustained chronically in skeletal muscle.

scholarly journals Response of skeletal muscle protein synthesis to insulin in suckling pigs decreases with development

1998 ◽  
Vol 275 (4) ◽  
pp. E602-E609 ◽  
Author(s):  
Diane Wray-Cahen ◽  
Hanh V. Nguyen ◽  
Douglas G. Burrin ◽  
Philip R. Beckett ◽  
Marta L. Fiorotto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Skeletal Muscle Protein ◽  
Protein Deposition ◽  
Skeletal Muscle Protein Synthesis ◽  
Elevated Rate

The elevated rate of muscle protein deposition in the neonate is largely due to an enhanced stimulation of skeletal muscle protein synthesis by feeding. To examine the role of insulin in this response, hyperinsulinemic-euglycemic-amino acid clamps were performed in 7- and 26-day-old pigs. Pigs were infused with 0, 30, 100, or 1,000 ng ⋅ kg−0.66 ⋅ min−1of insulin to mimic the plasma insulin levels observed under fasted, fed, refed, and supraphysiological conditions, respectively. Whole body amino acid disposal was determined from the rate of infusion of an amino acid mixture necessary to maintain plasma essential amino acid concentrations near their basal fasting levels. A flooding dose ofl-[4-3H]phenylalanine was used to measure skeletal muscle protein synthesis. Whole body amino acid disposal increased progressively as the insulin infusion rate increased, and this response was greater in 7- than in 26-day-old pigs. Skeletal muscle protein synthesis was stimulated by insulin, and this response was maximal at a low insulin infusion rate (30 ng ⋅ kg−0.66 ⋅ min−1). The stimulation of muscle protein synthesis by insulin was also greater in 7- than in 26- day-old pigs. These data suggest that muscle protein synthesis is more sensitive to insulin than whole body amino acid disposal. The results further suggest that insulin is a central regulatory factor in the elevated rate of muscle protein deposition and the increased response of skeletal muscle protein synthesis to feeding in the neonate.

scholarly journals Continuous Feeding Does Not Blunt Skeletal Muscle Protein Synthesis and Lean Growth Compared to Intermittent Bolus Feeding in the Preterm Piglet (OR26-06-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Marko Rudar ◽  
Jane Naberhuis ◽  
Hanh Nguyen ◽  
Agus Suryawan ◽  
Candace Style ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Protein Synthesis ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Feeding Strategies ◽  
Intermittent Bolus ◽  
Lean Growth ◽  
Continuous Feeding ◽  
The Impact

Abstract Objectives Refining early feeding strategies for premature infants is essential for mitigating adverse outcomes of prematurity. In neonatal term piglets, continuous feeding blunts growth compared to intermittent bolus feeding. Our objective was to determine the impact of feeding modality on lean growth in preterm pigs. We hypothesized that intermittent bolus feeding can mitigate low lean growth rates in preterm neonates compared to continuous feeding. Methods Pigs obtained by C-section (105 d gestation; 952 ± 205 g body weight) were fitted with an umbilical artery catheter (later replaced with jugular vein catheter) and an orogastric tube for parenteral and enteral nutrition, respectively. Pigs were assigned to continuous (CONT; 7.5 mL/[kg·h]) or intermittent bolus (INT; 30 mL/kg every 4 h over 15 min) feeding for 21 d. Pigs initially received parenteral nutrition and were advanced to full oral feeds over 6 d (220 kcal/kg and 16 g/kg protein per day). Body composition (by DXA), plasma insulin, and skeletal muscle anabolic signaling and fractional protein synthesis rates (PS; L-[ring-2H5]phenylalanine) were determined in INT pigs in the postabsorptive (before a meal, INT-PA; n = 13) and postprandial (after a meal, INT-PP; n = 16) states and in CONT pigs (n = 14). Results Body weight gain, lean mass, and fat mass did not differ between INT and CONT pigs. Insulin was lower before feeding for INT pigs than CONT pigs (P < 0.05). Insulin increased with feeding for INT pigs and exceeded that of CONT pigs at 30 and 60 min (P < 0.01) before returning to baseline levels at 240 min. In the longissimus dorsi (LD), gastrocnemius, and soleus muscles, the abundance of the eIF4E·eIF4G complex, which is required for translation initiation, was greater in INT-PP and CONT pigs than INT-PA pigs (P < 0.01), but did not differ between INT-PP and CONT pigs. PS in the LD muscle was greater in INT-PP pigs than INT-PA pigs (P < 0.01), but did not differ between INT-PP and CONT pigs. Conclusions Continuous feeding does not blunt translation initiation and protein synthesis in skeletal muscle compared to intermittent bolus feeding in preterm piglets. The resulting absence of enhanced lean growth with intermittent bolus compared to continuous feeding contrasts with term piglets and may be a consequence of prematurity. Funding Sources USDA CRIS 6250-51000-055, NIH HD072891, and USDA NIFA 2013-67015-20438.

scholarly journals Viscera and muscle protein synthesis in neonatal pigs is increased more by intermittent bolus than by continuous feeding

2013 ◽  
Vol 74 (2) ◽  
pp. 154-162 ◽  
Author(s):  
Samer W. El-Kadi ◽  
María C. Gazzaneo ◽  
Agus Suryawan ◽  
Renán A. Orellana ◽  
Roberto Murgas Torrazza ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Neonatal Pigs ◽  
Intermittent Bolus ◽  
Continuous Feeding

Insulin fails to stimulate muscle protein synthesis in sepsis despite unimpaired signaling to 4E-BP1 and S6K1

2001 ◽  
Vol 281 (5) ◽  
pp. E1045-E1053 ◽  
Author(s):  
Thomas C. Vary ◽  
Leonard S. Jefferson ◽  
Scot R. Kimball
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Insulin Signaling ◽  
Insulin Action ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Translation ◽  
Initiation Factor ◽  
S6 Kinase ◽  
Eif4f Complex

Induction of sepsis in rats causes an inhibition of protein synthesis in skeletal muscle that is resistant to the stimulatory actions of insulin. To gain a better understanding of the underlying reason for this lack of response, the present study was undertaken to investigate sepsis-induced alterations in insulin signaling to regulatory components of mRNA translation. Experiments were performed in perfused hindlimb preparations from rats 5 days after induction of a septic abscess. Sepsis resulted in a 50% reduction in protein synthesis in the gastrocnemius. Protein synthesis in muscles from septic rats, but not controls, was unresponsive to stimulation by insulin. The insulin-induced hyperphosphorylation response of the translation repressor protein 4E-binding protein 1 (4E-BP1) and of the 70-kDa S6 kinase (S6K1) (1), two targets of insulin action on mRNA translation, was unimpaired in gastrocnemius of septic rats. Hyperphosphorylation of 4E-BP1 in response to insulin resulted in its dissociation from the inactive eukaryotic initiation factor (eIF)4E · 4E-BP1 complex in both control and septic rats. However, assembly of the active eIF4F complex as assessed by the association of eIF4E with eIF4G did not follow the pattern predicted by the increased availability of eIF4E resulting from changes in the phosphorylation of 4E-BP1. Indeed, sepsis caused a dramatic reduction in the amount of eIF4G associated with eIF4E in the presence or absence of insulin. Thus the inability of insulin to stimulate protein synthesis during sepsis may be related to a defect in signaling to a step in translation initiation involved in assembly of an active eIF4F complex.

scholarly journals Intermittent bolus feeding does not enhance protein synthesis, myonuclear accretion, or lean growth more than continuous feeding in a premature piglet model

2021 ◽  
Author(s):  
Marko Rudar ◽  
Jane K. Naberhuis ◽  
Agus Suryawan ◽  
Hanh V. Nguyen ◽  
Barbara Stoll ◽  
...  
Keyword(s):  
Body Composition ◽  
Protein Synthesis ◽  
Satellite Cell ◽  
Muscle Protein ◽  
Body Weight Gain ◽  
Postnatal Life ◽  
Cell Abundance ◽  
Intermittent Bolus ◽  
Lean Growth ◽  
Continuous Feeding

Optimizing enteral nutrition for premature infants may help mitigate extrauterine growth restriction and adverse chronic health outcomes. Previously, we showed in neonatal pigs born at term that lean growth is enhanced by intermittent bolus compared to continuous feeding. The objective was to determine if prematurity impacts how body composition, muscle protein synthesis, and myonuclear accretion respond to feeding modality. Following preterm delivery, pigs were fed equivalent amounts of formula delivered either as intermittent boluses (INT; n = 30) or continuously (CONT; n = 14) for 21 days. Body composition was measured by DXA and muscle growth was assessed by morphometry, myonuclear accretion, and satellite cell abundance. Tissue anabolic signaling and fractional protein synthesis rates were determined in INT pigs in postabsorptive (INT-PA) and postprandial (INT-PP) states and in CONT pigs. Body weight gain and composition did not differ between INT and CONT pigs. Longissimus dorsi (LD) protein synthesis was 34% greater in INT-PP than INT-PA pigs (P < 0.05) but was not different between INT-PP and CONT pigs. Phosphorylation of 4EBP1 and S6K1 and eIF4E·eIF4G abundance in LD paralleled changes in LD protein synthesis. Satellite cell abundance, myonuclear accretion, and fiber cross-sectional area in LD did not differ between groups. These results suggest that, unlike pigs born at term, intermittent bolus feeding does not enhance lean growth more than continuous feeding in pigs born preterm. Premature birth attenuates the capacity of skeletal muscle to respond to cyclical surges in insulin and amino acids with intermittent feeding in early postnatal life.

Somatotropin increases protein balance by lowering body protein degradation in fed, growing pigs

2000 ◽  
Vol 278 (3) ◽  
pp. E477-E483 ◽  
Author(s):  
Rhonda C. Vann ◽  
Hanh V. Nguyen ◽  
Peter J. Reeds ◽  
Douglas G. Burrin ◽  
Marta L. Fiorotto ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Growing Pigs ◽  
Whole Body ◽  
Plasma Urea ◽  
Body Protein ◽  
Fed State ◽  
Protein Deposition ◽  
Leucine Oxidation ◽  
Urea Production

Somatotropin (ST) administration enhances protein deposition in well-nourished, growing animals. To determine whether the anabolic effect is due to an increase in protein synthesis or a decrease in proteolysis, pair-fed, weight-matched (∼20 kg) growing swine were treated with porcine ST (150 μg ⋅ kg− 1 ⋅ day− 1, n = 6) or diluent ( n = 6) for 7 days. Whole body leucine appearance (Ra), nonoxidative leucine disposal (NOLD), urea production, and leucine oxidation, as well as tissue protein synthesis (Ks), were determined in the fed steady state using primed continuous infusions of [13C]leucine, [13C]bicarbonate, and [15N2]urea. ST treatment increased the efficiency with which the diet was used for growth. ST treatment also increased plasma insulin-like growth factor I (+100%) and insulin (+125%) concentrations and decreased plasma urea nitrogen concentrations (−53%). ST-treated pigs had lower leucine Ra (−33%), leucine oxidation (−63%), and urea production (−70%). However, ST treatment altered neither NOLD nor Ks in the longissimus dorsi, semitendinosus, or gastrocnemius muscles, liver, or jejunum. The results suggest that in the fed state, ST treatment of growing swine increases protein deposition primarily through a suppression of protein degradation and amino acid catabolism rather than a stimulation of protein synthesis.

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