scholarly journals Lower Synthesis and Higher Catabolism of Liver and Muscle Protein Compensate for Amino Acid Deficiency in Severely Protein-Restricted Growing Rat

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 518-518
Author(s):  
Gaëtan Roisné-Hamelin ◽  
Joanna Moro ◽  
Nicolas Delhaye ◽  
Juliane Calvez ◽  
Catherine Chaumontet ◽  
...  
Keyword(s):  
Body Weight ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Protein Restriction ◽  
The Body ◽  
Synthesis Rate ◽  
Growing Rats ◽  
Initiation Of Translation ◽  
Ubiquitin Proteasome

Abstract Objectives Severely low-protein (LP) diets induce a decrease in body weight and an increase in relative food including intake (FI) in rat. In the liver, changes in anabolic and catabolic protein pathways could transitorily participate to compensate for amino acid (AA) deficiency. The present study investigated these liver and muscle protein metabolic pathways on LP diet fed growing rats. Methods Growing rats were fed for three weeks different diets containing 3–5–8–12–15 or 20% energy from milk protein. Body weight and FI were measured daily. At the end of the experiment, rats were injected with 13C valine and tissues and biological fluids were collected for gene expression measurement, blood AA UPLC analysis and protein synthesis rate determination in liver and muscle. Statistical analysis was done by 1- or 2-factor ANOVA, when data were repeated. Results P3, P5 and P8% diets resulted in significant growth retardation and significant decrease in lean mass. Severe protein deficiency induced a decrease in the rate of protein synthesis in the liver and muscle. In addition, the results showed activation of the GCN2 pathway, via ATF4-CHOP-TRB3 both in the liver and in the muscle, which suggests the inhibition of the initiation of translation at the level of the binding of the RNAt-Met. Liver proteolytic pathways were up-regulated including the ubiquitin-proteasome, the caspase system and the autophagy. In muscle, both the ubiquitin-proteasome pathway, and autophagy were increased as well as the calpain system. The GCN2 pathway, via ATF4-CHOP-TRB3 was activated in both liver and muscle, confirming the activation of protein degradation by the ubiquitin-proteasome pathways, and autophagy. In portal vein, indispensable AA were lower in severe protein deficient diet whereas in vena cava no difference was observed. Conclusions Severe protein restriction lowered protein synthesis and activated protein catabolism in both liver and muscle whereas no effect was observed for moderate protein restriction. These results confirm that the liver and muscle play a major role in supplying the body with indispensable AA in response to severe protein restriction. Funding Sources This study was funded by the doctoral school ABIES and AlimH-INRAE department.

The single-biopsy approach in determining protein synthesis in human slow-turning-over tissue: use of flood-primed, continuous infusion of amino acid tracers

2014 ◽  
Vol 306 (11) ◽  
pp. E1330-E1339 ◽  
Author(s):  
Lars Holm ◽  
Søren Reitelseder ◽  
Kasper Dideriksen ◽  
Rie H. Nielsen ◽  
Jacob Bülow ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Continuous Infusion ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Tissue Biopsy ◽  
Infusion Protocol

Muscle protein synthesis (MPS) rate is determined conventionally by obtaining two or more tissue biopsies during a primed, continuous infusion of a stable isotopically labeled amino acid. The purpose of the present study was to test whether tracer priming given as a flooding dose, thereby securing an instantaneous labeling of the tissue pools of free tracee amino acids, followed by a continuous infusion of the same tracer to maintain tracer isotopic steady state, could be used to determine the MPS rate over a prolonged period of time by obtaining only a single tissue biopsy. We showed that the tracer from the flood prime appeared immediately in the muscle free pool of amino acids and that this abundance could be kept constant by a subsequent continuous infusion of the tracer. When using phenylalanine as tracer, the flood-primed, continuous infusion protocol does not stimulate the MPS rate per se. In conclusion, the flood-primed, continuous infusion protocol using phenylalanine as tracer can validly be used to measure the protein synthesis rate in human in vivo experiments by obtaining only a single tissue biopsy after a prolonged infusion period.

scholarly journals Reducing plasma HIV RNA improves muscle amino acid metabolism

2005 ◽  
Vol 288 (1) ◽  
pp. E278-E284 ◽  
Author(s):  
Kevin E. Yarasheski ◽  
Samuel R. Smith ◽  
William G. Powderly
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Hiv Rna ◽  
Muscle Protein Synthesis Rate

We reported (Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Horgan MM, and Powderly WG. Am J Physiol Endocrinol Metab 275: E577–E583, 1998) that AIDS muscle wasting was associated with an inappropriately low rate of muscle protein synthesis and an elevated glutamine rate of appearance (Ra Gln). We hypothesized that high plasma HIV RNA caused dysregulation of muscle amino acid metabolism. We determined whether a reduction in HIV RNA (≥1 log) increased muscle protein synthesis rate and reduced Ra Gln and muscle proteasome activity in 10 men and 1 woman (22–57 yr, 60–108 kg, 17–33 kg muscle) with advanced HIV (CD4 = 0–311 cells/μl; HIV RNA = 10–375 × 103 copies/ml). We utilized stable isotope tracer methodologies ([13C]Leu and [15N]Gln) to measure the fractional rate of mixed muscle protein synthesis and plasma Ra Gln in these subjects before and 4 mo after initiating their first or a salvage antiretroviral therapy regimen. After treatment, median CD4 increased (98 vs. 139 cells/μl, P = 0.009) and median HIV RNA was reduced (155,828 vs. 100 copies/ml, P = 0.003). Mixed muscle protein synthesis rate increased (0.062 ± 0.005 vs. 0.078 ± 0.006%/h, P = 0.01), Ra Gln decreased (387 ± 33 vs. 323 ± 15 μmol·kg fat-free mass−1·h−1, P = 0.04), and muscle proteasome chymotrypsin-like catalytic activity was reduced 14% ( P = 0.03). Muscle mass was only modestly increased (1 kg, P = not significant). We estimated that, for each 10,000 copies/ml reduction in HIV RNA, ∼3 g of additional muscle protein are synthesized per day. These findings suggest that reducing HIV RNA increases muscle protein synthesis and reduces muscle proteolysis, but muscle protein synthesis relative to whole body protein synthesis rate is not restored to normal, so muscle mass is not substantially increased.

Measurement of human mixed muscle protein fractional synthesis rate depends on the choice of amino acid tracer

2007 ◽  
Vol 293 (3) ◽  
pp. E666-E671 ◽  
Author(s):  
Gordon I. Smith ◽  
Dennis T. Villareal ◽  
Bettina Mittendorfer
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Tissue ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Fat Free Mass ◽  
Synthesis Rate ◽  
Tissue Fluid ◽  
Fractional Synthesis Rate ◽  
Fractional Synthesis

The goal of this study was to discover whether using different tracers affects the measured rate of muscle protein synthesis in human muscle. We therefore measured the mixed muscle protein fractional synthesis rate (FSR) in the quadriceps of older adults during basal, postabsorptive conditions and mixed meal feeding (70 mg protein·kg fat-free mass−1·h−1 × 2.5 h) by simultaneous intravenous infusions of [5,5,5-2H3]leucine and either [ring-13C6]phenylalanine or [ring-2H5]phenylalanine and analysis of muscle tissue samples by gas chromatography-mass spectrometry. Both the basal FSR and the FSR during feeding were ∼20% greater ( P < 0.001) when calculated from the leucine labeling in muscle tissue fluid and proteins (fasted: 0.063 ± 0.005%/h; fed: 0.080 ± 0.007%/h) than when calculated from the phenylalanine enrichment data (0.051 ± 0.004 and 0.066 ± 0.005%/h, respectively). The feeding-induced increase in the FSR (∼20%; P = 0.011) was not different with leucine and phenylalanine tracers ( P = 0.69). Furthermore, the difference between the leucine- and phenylalanine-derived FSRs was independent of the phenylalanine isotopomer used ( P = 0.92). We conclude that when using stable isotope-labeled tracers and the classic precursor product model to measure the rate of muscle protein synthesis, absolute rates of muscle protein FSR differ significantly depending on the tracer amino acid used; however, the anabolic response to feeding is independent of the tracer used. Thus different precursor amino acid tracers cannot be used interchangeably for the evaluation of muscle protein synthesis, and data from studies using different tracer amino acids can be compared qualitatively but not quantitatively.

Sustained Modifications of Protein Metabolism in Various Tissues in a Rat Model of Long-Lasting Sepsis

1998 ◽  
Vol 94 (4) ◽  
pp. 413-423 ◽  
Author(s):  
Denis Breuillé ◽  
Maurice Arnal ◽  
Fabienne Rambourdin ◽  
Gérard Bayle ◽  
Didier Levieux ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Acute Phase ◽  
Muscle Protein ◽  
Plasma Concentrations ◽  
Chronic Phase ◽  
The Body ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Liver Protein ◽  
Skin Protein

1. Sepsis was induced in rats by an intravenous injection of live bacteria. Infected and pair-fed animals were studied before the infection, in an acute septic phase (day 2 post-infection), in a chronic septic phase (day 6) and in a late septic phase (day 10). Protein synthesis rates were measured in vivo after administration of a flooding dose of l[1-13C]valine. 2. During the acute phase, muscle protein loss associated with infection resulted from both a decrease in protein synthesis and an increase in proteolysis. During the chronic phase and the late phase, the increase of proteolysis in infected rats as compared with pair-fed animals persisted, worsening muscle atrophy. Skin protein synthesis rates were not significantly modified by infection. However, skin protein content decreased 6 and 10 days after infection, suggesting an increased proteolysis in response to sepsis. 3. Protein synthesis in liver of infected rats was twice that of pair-fed animals. Liver protein synthesis remained elevated in infected rats compared with pair-fed animals until day 10. Hypoalbuminaemia and high plasma concentrations of fibrinogen were evident at all periods studied. α2-Macroglobulin and α1-acid glycoprotein reached peak concentrations during the acute phase (concentrations increased 50 times in infected rats). On day 10, the levels of these proteins were still about 12-fold higher. 4. Protein synthesis rates were significantly increased in the digestive tract and lung of infected rats compared with pair-fed groups on days 2 and 6, but were similar in the two groups on day 10 postinfection. The fractional protein synthesis rate was increased 3-fold over the entire experimental period in the spleen. 5. The results show that sepsis stimulates protein synthesis in various tissues over a long time, and that skin, like muscle, can provide amino acids to the rest of the body.

Comparison of Arterial-Venous Balance and Tracer Incorporation Methods for Measuring Muscle Fractional Synthesis and Fractional Breakdown Rates

2021 ◽  
Author(s):  
Joshua L Hudson ◽  
Matthew Cotter ◽  
David N Herndon ◽  
Robert R Wolfe ◽  
Elisabet Børsheim
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Stable Isotope ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Constant Infusion ◽  
Synthesis Rate ◽  
Skeletal Muscle Protein ◽  
Breakdown Rates ◽  
Fractional Synthesis

Abstract Loss of muscle mass in response to injury or immobilization impairs functional capacity and metabolic health, thus hindering rehabilitation. Stable isotope techniques are powerful in determining skeletal muscle protein fluxes. Traditional tracer incorporation methods to measure muscle protein synthesis and breakdown are cumbersome and invasive to perform in vulnerable populations such as children. To circumvent these issues, a two-bolus stable isotope amino acid method has been developed; although, measured rates of protein synthesis and breakdown have not been validated simultaneously against an accepted technique such as the arterial-venous balance method. The purpose of the current analysis was to provide preliminary data from the simultaneous determination of the arteriovenous balance and two-bolus tracer incorporation methods on muscle fractional synthesis and breakdown rates in children with burns. Five were administered a primed-constant infusion of L-[ 15N]Threonine for 180 minutes (Prime: 8 µmol/kg; constant: 0.1 µmol·kg -1·min -1). At 120 and 150 minutes, bolus injections of L-[ring- 13C6]Phenylalanine and L-[ 15N]Phenylalanine (50 µmol/kg each) were administered, respectively. Blood and muscle tissue samples were collected to assess mixed muscle protein synthesis and breakdown rates. The preliminary results from this study indicate there is no difference in either fractional synthesis rate (mean ± SD; arteriovenous balance: 0.19 ± 0.17 %/h; tracer incorporation: 0.14 ± 0.08 %/h; P = 0.42) or fractional breakdown rate (arteriovenous balance: 0.29 ± 0.22 %/h; tracer incorporation: 0.23 ± 0.14 %/h; P = 0.84) between methods. These data support the validity of both methods in quantifying muscle amino acid kinetics; however, the results are limited and adequately powered research is still required.

Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation

2007 ◽  
Vol 293 (5) ◽  
pp. E1416-E1425 ◽  
Author(s):  
Renán A. Orellana ◽  
Asumthia Jeyapalan ◽  
Jeffery Escobar ◽  
Jason W. Frank ◽  
Hanh V. Nguyen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Neonatal Pigs

In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study, we determined the effect of amino acids on protein synthesis in skeletal muscle and other tissues in septic neonates. Overnight-fasted neonatal pigs were infused with endotoxin (LPS, 0 and 10 μg·kg−1·h−1), whereas glucose and insulin were maintained at fasting levels; amino acids were clamped at fasting or fed levels. In the presence of fasting insulin and amino acids, LPS reduced protein synthesis in longissimus dorsi (LD) and gastrocnemius muscles and increased protein synthesis in the diaphragm, but had no effect in masseter and heart muscles. Increasing amino acids to fed levels accelerated muscle protein synthesis in LD, gastrocnemius, masseter, and diaphragm. LPS stimulated protein synthesis in liver, lung, spleen, pancreas, and kidney in fasted animals. Raising amino acids to fed levels increased protein synthesis in liver of controls, but not LPS-treated animals. The increase in muscle protein synthesis in response to amino acids was associated with increased mTOR, 4E-BP1, and S6K1 phosphorylation and eIF4G-eIF4E association in control and LPS-infused animals. These findings suggest that amino acids stimulate skeletal muscle protein synthesis during acute endotoxemia via mTOR-dependent ribosomal assembly despite reduced basal protein synthesis rates in neonatal pigs. However, provision of amino acids does not further enhance the LPS-induced increase in liver protein synthesis.

scholarly journals Maternal protein reserves and their influence on lactational performance in rats 4. Tissue protein synthesis and turnover associated with mobilization of maternal protein

1994 ◽  
Vol 72 (6) ◽  
pp. 831-844 ◽  
Author(s):  
A.P. Pine ◽  
N.S. Jessop ◽  
G.F. Allan ◽  
J.D. Oldham
Keyword(s):  
Protein Synthesis ◽  
Dietary Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Protein Restriction ◽  
Synthesis Rate ◽  
Liver Protein ◽  
Tissue Protein ◽  
Stage Of Lactation ◽  
Tissue Protein Synthesis

The present study was undertaken to investigate the changes in muscle protein turnover involved in the rapid mobilization of protein in rats subjected to severe protein restriction during lactation. Estimates of mammary gland and liver protein synthesis were also made during lactation. Multiparous female Sprague-Dawley rats, caged individually following mating, were offered a high-protein diet (H; 215 g crude protein (N - 6·25; CP)/kg dry matter (DM)) ad lib. until parturition. Following parturition, half the females continued to receive diet H, whilst the remainder were offered a diet low in protein (L; 90 g CP/kg DM) ad lib. On days 2, 4, 8 and 12 of lactation, groups of females were used in the estimation of tissue protein synthesis (flooding dose of [3H]phenylalanine) immediately after a milk sample had been obtained. Rates of muscle protein synthesis were unchanged during lactation in group H. The feeding of diet L during lactation reduced the muscle protein synthesis on day 12 to rates that were lower than group H and also the rate on diet L on day 2 (P 0·01). However, this fall in muscle protein synthesis was not rapid and muscle fractional synthesis rate (FSR) was different from group H only from day 8 (P 0·05). Estimated rates of mammary protein synthesis appeared to be generally unchanged by dietary treatment or stage of lactation. Liver FSR was also unchanged by dietary protein supply or stage of lactation. The effect of dietary protein restriction on liver size and protein content during lactation influenced liver absolute synthesis rate (ASR), and on days 8 and 12 of lactation liver ASR was lower in group L than in group H (P 0·001). The loss of muscle protein in rats fed on diet L during lactation (133 mg) occurred mainly between days 2 and 8 of lactation and was primarily associated with a dramatic increase in degradation (13·0% per d), with the decline in synthesis having a much smaller role. A decline in muscle protein degradation during the latter half of lactation was part of the mechanism that prevented excessive muscle protein catabolism. It is thought that the estimation of mammary protein synthesis in the present study was impaired by the milk sampling procedure previously used.

Isoleucine increases muscle mass through promoting myogenesis and intramyocellular fat deposition

2021 ◽  
Author(s):  
Shuge Liu ◽  
Yunmei Sun ◽  
Rui Zhao ◽  
Yingqian Wang ◽  
Wanrong Zhang ◽  
...  
Keyword(s):  
Body Weight ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Vital Role ◽  
Fat Deposition ◽  
Branched Chain Amino Acid ◽  
Branched Chain

Isoleucine (Ile), as a branched-chain amino acid (BCAA), has a vital role in regulating body weight and muscle protein synthesis.

scholarly journals Comprehensive assessment of post-prandial protein handling by the application of intrinsically labelled protein in vivo in human subjects

2021 ◽  
pp. 1-9
Author(s):  
Jorn Trommelen ◽  
Andrew M. Holwerda ◽  
Philippe J. M. Pinckaers ◽  
Luc J. C. van Loon
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Stable Isotope ◽  
Dietary Protein ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Human Subjects ◽  
Whole Body ◽  
Body Protein

All human tissues are in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates. It has been well-established that protein ingestion stimulates skeletal muscle and whole-body protein synthesis. Stable isotope-labelled amino acid methodologies are commonly applied to assess the various aspects of protein metabolism in vivo in human subjects. However, to achieve a more comprehensive assessment of post-prandial protein handling in vivo in human subjects, intravenous stable isotope-labelled amino acid infusions can be combined with the ingestion of intrinsically labelled protein and the collection of blood and muscle tissue samples. The combined application of ingesting intrinsically labelled protein with continuous intravenous stable isotope-labelled amino acid infusion allows the simultaneous assessment of protein digestion and amino acid absorption kinetics (e.g. release of dietary protein-derived amino acids into the circulation), whole-body protein metabolism (whole-body protein synthesis, breakdown and oxidation rates and net protein balance) and skeletal muscle metabolism (muscle protein fractional synthesis rates and dietary protein-derived amino acid incorporation into muscle protein). The purpose of this review is to provide an overview of the various aspects of post-prandial protein handling and metabolism with a focus on insights obtained from studies that have applied intrinsically labelled protein under a variety of conditions in different populations.

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