P.25 Mechanisms behind feeding induced stimulation of skeletal muscle protein synthesis following undernutrition

The rapid gain in skeletal muscle mass in the neonate is associated with a marked elevation in skeletal muscle protein synthesis in response to feeding. The feeding-induced response decreases with development. To determine whether the response to feeding is regulated at the level of translation initiation, the expression, phosphorylation, and function of a number of eukaryotic initiation factors (eIF) were examined. Pigs at 7 and 26 days of age were either fasted overnight or fed porcine milk after an overnight fast. In muscle of 7-day-old pigs, the hyperphosphorylated form of the eIF4E repressor protein, 4E-binding protein 1 (4E-BP1), was undetectable in the fasting state but rose to 60% of total 4E-BP1 after feeding; eIF4E phosphorylation was unaffected by feeding status. The amount of eIF4E in the inactive 4E-BP1 · eIF4E complex was reduced by 80%, and the amount of eIF4E in the active eIF4E · eIF4G complex was increased 14-fold in muscle of 7-day-old pigs after feeding. The amount of 70-kDa ribosomal protein S6 (p70S6) kinase in the hyperphosphorylated form rose 2.5-fold in muscle of 7-day-old pigs after feeding. Each of these feeding-induced responses was blunted in muscle of 26-day-old pigs. eIF2B activity in muscle was unaffected by feeding status but decreased with development. Feeding produced similar changes in eIF characteristics in liver and muscle; however, the developmental changes in liver were not as apparent as in skeletal muscle. Thus the results demonstrate that the developmental change in the acute stimulation of skeletal muscle protein synthesis by feeding is regulated by the availability of eIF4E for 48S ribosomal complex formation. The results further suggest that the overall developmental decline in skeletal muscle protein synthesis involves regulation by eIF2B.

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Stimulation of muscle protein synthesis by somatotropin in pigs is independent of the somatotropin-induced increase in circulating insulin

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90253.2008 ◽

2008 ◽

Vol 295 (1) ◽

pp. E187-E194 ◽

Cited By ~ 3

Author(s):

Fiona A. Wilson ◽

Renán A. Orellana ◽

Agus Suryawan ◽

Hanh V. Nguyen ◽

Asumthia S. Jeyapalan ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Translation Initiation ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Growing Pigs ◽

Initiation Factor ◽

Skeletal Muscle Protein ◽

Skeletal Muscle Protein Synthesis ◽

Stimulation Of

Chronic treatment of growing pigs with porcine somatotropin (pST) promotes protein synthesis and doubles postprandial levels of insulin, a hormone that stimulates translation initiation. This study aimed to determine whether the pST-induced increase in skeletal muscle protein synthesis was mediated through an insulin-induced stimulation of translation initiation. After 7–10 days of pST (150 μg·kg−1·day−1) or control saline treatment, pancreatic glucose-amino acid clamps were performed in overnight-fasted pigs to reproduce 1) fasted (5 μU/ml), 2) fed control (25 μU/ml), and 3) fed pST-treated (50 μU/ml) insulin levels while glucose and amino acids were maintained at baseline fasting levels. Fractional protein synthesis rates and indexes of translation initiation were examined in skeletal muscle. Effectiveness of pST treatment was confirmed by reduced urea nitrogen and elevated insulin-like growth factor I levels in plasma. Skeletal muscle protein synthesis was independently increased by both insulin and pST. Insulin increased the phosphorylation of protein kinase B and the downstream effectors of the mammalian target of rapamycin, ribosomal protein S6 kinase, and eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1). Furthermore, insulin reduced inactive 4E-BP1·eIF4E complex association and increased active eIF4E·eIF4G complex formation, indicating enhanced eIF4F complex assembly. However, pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of skeletal muscle protein synthesis in growing pigs is independent of the insulin-associated activation of translation initiation.

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Leucine stimulation of skeletal muscle protein synthesis during prolonged leucine infusion is dependent on amino acid availability

The FASEB Journal ◽

10.1096/fasebj.20.4.a162 ◽

2006 ◽

Vol 20 (4) ◽

Author(s):

Jeffery Escobar ◽

Jason W Frank ◽

Agus Suryawan ◽

Hanh V Nguyen ◽

Teresa A Davis

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Amino Acid ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Skeletal Muscle Protein ◽

Amino Acid Availability ◽

Skeletal Muscle Protein Synthesis ◽

Stimulation Of

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Anorexia decreases skeletal muscle protein synthesis in cancer cachexia

Clinical Nutrition ◽

10.1016/0261-5614(82)90252-7 ◽

1982 ◽

Vol 1 ◽

pp. 131

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Cancer Cachexia ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Skeletal Muscle Protein ◽

Skeletal Muscle Protein Synthesis

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Effects of leucine-enriched essential amino acid and whey protein bolus dosing upon skeletal muscle protein synthesis at rest and after exercise in older women

Clinical Nutrition ◽

10.1016/j.clnu.2017.09.008 ◽

2018 ◽

Vol 37 (6) ◽

pp. 2011-2021 ◽

Cited By ~ 31

Author(s):

Daniel J. Wilkinson ◽

Syed S.I. Bukhari ◽

Bethan E. Phillips ◽

Marie C. Limb ◽

Jessica Cegielski ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Amino Acid ◽

Older Women ◽

Whey Protein ◽

Essential Amino Acid ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Skeletal Muscle Protein ◽

Skeletal Muscle Protein Synthesis

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Resistance exercise maintains skeletal muscle protein synthesis during bed rest

Journal of Applied Physiology ◽

10.1152/jappl.1997.82.3.807 ◽

1997 ◽

Vol 82 (3) ◽

pp. 807-810 ◽

Cited By ~ 147

Author(s):

Arny A. Ferrando ◽

Kevin D. Tipton ◽

Marcas M. Bamman ◽

Robert R. Wolfe

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Resistance Training ◽

Resistance Exercise ◽

Lean Body Mass ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Bed Rest ◽

Skeletal Muscle Protein ◽

Skeletal Muscle Protein Synthesis

Ferrando, Arny A., Kevin D. Tipton, Marcas M. Bamman, and Robert R. Wolfe. Resistance exercise maintains skeletal muscle protein synthesis during bed rest. J. Appl. Physiol. 82(3): 807–810, 1997.—Spaceflight results in a loss of lean body mass and muscular strength. A ground-based model for microgravity, bed rest, results in a loss of lean body mass due to a decrease in muscle protein synthesis (MPS). Resistance training is suggested as a proposed countermeasure for spaceflight-induced atrophy because it is known to increase both MPS and skeletal muscle strength. We therefore hypothesized that scheduled resistance training throughout bed rest would ameliorate the decrease in MPS. Two groups of healthy volunteers were studied during 14 days of simulated microgravity. One group adhered to strict bed rest (BR; n = 5), whereas a second group engaged in leg resistance exercise every other day throughout bed rest (BREx; n = 6). MPS was determined directly by the incorporation of infusedl-[ ring-13C6]phenylalanine into vastus lateralis protein. After 14 days of bed rest, MPS in the BREx group did not change and was significantly greater than in the BR group. Thus moderate-resistance exercise can counteract the decrease in MPS during bed rest.

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Growth hormone acutely stimulates forearm muscle protein synthesis in normal humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.260.3.e499 ◽

1991 ◽

Vol 260 (3) ◽

pp. E499-E504 ◽

Cited By ~ 22

Author(s):

D. A. Fryburg ◽

R. A. Gelfand ◽

E. J. Barrett

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Growth Hormone ◽

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Skeletal Muscle Protein ◽

Skeletal Muscle Protein Synthesis ◽

Igf I ◽

Normal Humans

The short-term effects of growth hormone (GH) on skeletal muscle protein synthesis and degradation in normal humans are unknown. We studied seven postabsorptive healthy men (age 18-23 yr) who received GH (0.014 micrograms.kg-1.min-1) via intrabrachial artery infusion for 6 h. The effects of GH on forearm amino acid and glucose balances and on forearm amino acid kinetics [( 3H]Phe and [14C]Leu) were determined after 3 and 6 h of the GH infusion. Forearm deep vein GH rose to 35 +/- 6 ng/ml in response to GH, whereas systemic levels of GH, insulin, and insulin-like growth factor I (IGF-I) were unchanged. Forearm glucose uptake did not change during the study. After 6 h, GH suppressed forearm net release (3 vs. 6 h) of Phe (P less than 0.05), Leu (P less than 0.01), total branched-chain amino acids (P less than 0.025), and essential neutral amino acids (0.05 less than P less than 0.1). The effect on the net balance of Phe and Leu was due to an increase in the tissue uptake for Phe (71%, P less than 0.05) and Leu (37%, P less than 0.005) in the absence of any significant change in release of Phe or Leu from tissue. In the absence of any change in systemic GH, IGF-I, or insulin, these findings suggest that locally infused GH stimulates skeletal muscle protein synthesis. These findings have important physiological implications for both the role of daily GH pulses and the mechanisms through which GH can promote protein anabolism.

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