scholarly journals The effects of endotoxaemia on protein metabolism in skeletal muscle and liver of fed and fasted rats

1986 ◽  
Vol 235 (2) ◽  
pp. 329-336 ◽  
Author(s):  
M M Jepson ◽  
J M Pell ◽  
P C Bates ◽  
D J Millward
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Synthesis Rate ◽  
Liver Protein ◽  
Fractional Synthesis Rate ◽  
Protein Mass ◽  
Fractional Synthesis ◽  
Fasted Rats

The response of muscle and liver protein metabolism to either a single or three successive daily injections of an endotoxin (Escherichia coli lipopolysaccharide, serotype 0127 B8; 1 mg/ml, 0.3 mg/100 g body wt.) was studied in vivo in the fed rat, and at 24 and 30 h after endotoxin treatment during fasting. In the fed rats there was a catabolic response in muscle, owing to a 60-100% increase in muscle protein degradation rate, and a 52% fall in the synthesis rate. Although there was a 20% decrease in food intake, the decrease in protein synthesis was to some extent independent of this, since rats treated with endotoxin and fasted also showed a lower rate of muscle protein synthesis, which was in excess of the decrease caused by fasting alone. The mechanism of this decreased protein synthesis involved decreased translational activity, since in both fed and fasted rats there was a decreased rate of synthesis per unit of RNA. This occurred despite the fact that insulin concentrations were either maintained or increased, in the fasted rats, to those observed in fed rats. In the liver total protein mass was increased in the fed rats by 16% at 24 h, and the fractional synthesis rate at that time was increased by 35%. In rats fasted after endotoxin treatment the liver protein mass was not decreased as it was in the control fasted rats, and the fractional synthesis rate was increased by 22%. In both cases the increased synthesis rate reflected an elevated hepatic RNA concentration. The extent of this increase in hepatic protein synthesis was sufficient at one point to compensate for the fall in estimated muscle protein synthesis, so that the sum total in the two tissues was maintained.

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.

scholarly journals The effects of breed and level of nutrition on whole-body and muscle protein metabolism in pure-bred Aberdeen Angus and Charolais beef steers

2000 ◽  
Vol 84 (3) ◽  
pp. 275-284 ◽  
Author(s):  
G. E. Lobley ◽  
K. D. Sinclair ◽  
C. M. Grant ◽  
L. Miller ◽  
D. Mantle ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Live Weight ◽  
Whole Body ◽  
Synthesis Rate ◽  
Eating Quality ◽  
Eye Muscle ◽  
Fractional Synthesis Rate ◽  
Fractional Synthesis

Eighteen pure-bred steers (live weight 350 kg) from each of two breeds, Aberdeen Angus (AA) and Charolais (CH), were split into three equal groups (six animals each) and offered three planes of nutrition during a 20-week period. The same ration formulation was offered to all animals with amounts adjusted at 3-week intervals to give predicted average weight gains of either 1·0 kg/d (M/M group) or 1·4 kg/d (H/H group). The remaining group (M/H) were offered the same amount of ration as the M/M group until 10 weeks before slaughter when the ration was increased to H. Data on animal performance, carcass characteristics and fibre-type composition in skeletal muscle are presented elsewhere (; ). On three occasions (17, 10 and 2 weeks before slaughter) the animals were transferred to metabolism stalls for 1 week, during which total urine collection for quantification of Nτ-methylhistidine (Nτ-MeH) elimination was performed for 4 d. On the last day, animals were infused for 11 h with [2H5] phenylalanine with frequent blood sampling (to allow determination of whole-body phenylalanine flux) followed by biopsies from m. longissimus lumborum and m. vastus lateralis to determine the fractional synthesis rate of mixed muscle protein. For both breeds, the absolute amount of Nτ-MeH eliminated increased with animal age or weight (P < 0·001) and was significantly greater for CH steers, at all intake comparisons, than for AA (P < 0·001). Estimates of fractional muscle breakdown rate (FBR; calculated from Nτ-MeH elimination and based on skeletal muscle as a fixed fraction of live weight) showed an age (or weight) decline for M/M and H/H groups of both breeds (P < 0·001). FBR was greater for the H/H group (P = 0·044). The M/H group also showed a lower FBR for the first two measurement periods (both at M intake) but increased when intake was raised to H. When allowance was made for differences in lean content (calculated from fat scores and eye muscle area in carcasses at the end of period 3), there were significant differences in muscle FBR with intake (P = 0·012) but not between breed. Whole-body protein flux (WBPF; g/d) based on plasma phenylalanine kinetics increased with age or weight (P < 0·001) and was similar between breeds. The WBPF was lower for M/M compared with H/H (P < 0·001) based on either total or per kg live weight0·75. Muscle protein fractional synthesis rate (FSR) declined with age for both breeds and tended to be higher at H/H compared with M intakes (intake × period effects, P < 0·05). Changing intake from M to H caused a significant increase (P < 0·001) in FSR. The FSR values for AA were significantly greater than for CH at comparable ages (P = 0·044). Although FSR and FBR responded to nutrition, these changes in protein metabolism were not reflected in differences in meat eating quality (Sinclair et al. 2000).

scholarly journals Lower recovery of muscle protein lost during starvation in old rats despite a stimulation of protein synthesis

1999 ◽  
Vol 277 (4) ◽  
pp. E608-E616 ◽  
Author(s):  
L. Mosoni ◽  
T. Malmezat ◽  
M. C. Valluy ◽  
M. L. Houlier ◽  
D. Attaix ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Age Groups ◽  
Liver Protein ◽  
Protein Mass ◽  
Old Rats ◽  
Proteolytic Pathways ◽  
Lower Recovery

Sarcopenia could result from the inability of an older individual to recover muscle lost during catabolic periods. To test this hypothesis, we compared the capacity of 5-day-refed 12- and 24-mo-old rats to recover muscle mass lost after 10 days without food. We measured gastrocnemius and liver protein synthesis with the flooding-dose method and also measured nitrogen balance, 3-methylhistidine excretion, and the gene expression of components of proteolytic pathways in muscle comparing fed, starved, and refed rats at each age. We show that 24-mo-old rats had an altered capacity to recover muscle proteins. Muscle protein synthesis, inhibited during starvation, returned to control values during refeeding in both age groups. The lower recovery in 24-mo-old rats was related to a lack of inhibition of muscle proteolysis during refeeding. The level of gene expression of components of the proteolytic pathways did not account for the variations in muscle proteolysis at both ages. In conclusion, this study highlights the role of muscle proteolysis in the lower recovery of muscle protein mass lost during catabolic periods.

scholarly journals Protein metabolism in the tumour-bearing mouse. Rates of protein synthesis in host tissues and in an Ehrlich ascites tumour at different stages in tumour growth

1989 ◽  
Vol 264 (3) ◽  
pp. 713-719 ◽  
Author(s):  
M N Lopes ◽  
P Black ◽  
A J Ashford ◽  
V M Pain
Keyword(s):  
Protein Synthesis ◽  
Food Intake ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Liver Protein ◽  
Humoral Factors ◽  
Ascites Tumour ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Tumour

We have investigated the time course of the changes in protein metabolism in skeletal muscle and liver in mice during the progression of growth of an Ehrlich ascites tumour. The rate of protein synthesis in muscle begins to fall very rapidly, and the decrease is clearly established by the time the tumour first becomes visible at 4 days after implantation of the cells. Liver protein synthesis increases substantially, and protein breakdown in muscle increases, but the onset of both these changes occurs later than the fall in muscle protein synthesis. A decrease in food intake in these animals occurs very rapidly after introduction of the cells. The fractional rate of protein synthesis in the tumour cells falls from 73%/day at 5 days to 26%/day at 12 days after injection, but on an absolute basis the rate of protein synthesis in the tumour at 5 days of growth is very small compared with that in muscle and liver. These results are consistent with the notion that the initial effects on muscle protein synthesis and food intake are brought about by humoral factors rather than as direct consequences of the metabolic demands of the growing tumour.

scholarly journals Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats

2016 ◽  
Vol 310 (6) ◽  
pp. E405-E417 ◽  
Author(s):  
Mahalakshmi Shankaran ◽  
Todd W. Shearer ◽  
Stephen A. Stimpson ◽  
Scott M. Turner ◽  
Chelsea King ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Androgen Receptor ◽  
Muscle Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Synthesis Rate ◽  
Muscle Proteins ◽  
Receptor Modulator ◽  
Fractional Synthesis

Biomarkers of muscle protein synthesis rate could provide early data demonstrating anabolic efficacy for treating muscle-wasting conditions. Androgenic therapies have been shown to increase muscle mass primarily by increasing the rate of muscle protein synthesis. We hypothesized that the synthesis rate of large numbers of individual muscle proteins could serve as early response biomarkers and potentially treatment-specific signaling for predicting the effect of anabolic treatments on muscle mass. Utilizing selective androgen receptor modulator (SARM) treatment in the ovariectomized (OVX) rat, we applied an unbiased, dynamic proteomics approach to measure the fractional synthesis rates (FSR) of 167–201 individual skeletal muscle proteins in triceps, EDL, and soleus. OVX rats treated with a SARM molecule (GSK212A at 0.1, 0.3, or 1 mg/kg) for 10 or 28 days showed significant, dose-related increases in body weight, lean body mass, and individual triceps but not EDL or soleus weights. Thirty-four out of the 94 proteins measured from the triceps of all rats exhibited a significant, dose-related increase in FSR after 10 days of SARM treatment. For several cytoplasmic proteins, including carbonic anhydrase 3, creatine kinase M-type (CK-M), pyruvate kinase, and aldolase-A, a change in 10-day FSR was strongly correlated ( r2 = 0.90–0.99) to the 28-day change in lean body mass and triceps weight gains, suggesting a noninvasive measurement of SARM effects. In summary, FSR of multiple muscle proteins measured by dynamics of moderate- to high-abundance proteins provides early biomarkers of the anabolic response of skeletal muscle to SARM.

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.

Epinephrine depletion exacerbates the fasting-induced protein breakdown in fast-twitch skeletal muscles

2013 ◽  
Vol 305 (12) ◽  
pp. E1483-E1494 ◽  
Author(s):  
Flávia A. Graça ◽  
Dawit A. P. Gonçalves ◽  
Wilian A. Silveira ◽  
Eduardo C. Lira ◽  
Valéria Ernestânia Chaves ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Skeletal Muscles ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Physiological Role ◽  
Protein Breakdown ◽  
Muscle Protein Metabolism ◽  
Fast Twitch ◽  
Fasted Rats

The physiological role of epinephrine in the regulation of skeletal muscle protein metabolism under fasting is unknown. We examined the effects of plasma epinephrine depletion, induced by adrenodemedullation (ADMX), on muscle protein metabolism in fed and 2-day-fasted rats. In fed rats, ADMX for 10 days reduced muscle mass, the cross-sectional area of extensor digitorum longus (EDL) muscle fibers, and the phosphorylation levels of Akt. In addition, ADMX led to a compensatory increase in muscle sympathetic activity, as estimated by the rate of norepinephrine turnover; this increase was accompanied by high rates of muscle protein synthesis. In fasted rats, ADMX exacerbated fasting-induced proteolysis in EDL but did not affect the low rates of protein synthesis. Accordingly, ADMX activated lysosomal proteolysis and further increased the activity of the ubiquitin (Ub)-proteasome system (UPS). Moreover, expression of the atrophy-related Ub ligases atrogin-1 and MuRF1 and the autophagy-related genes LC3b and GABARAPl1 were upregulated in EDL muscles from ADMX-fasted rats compared with sham-fasted rats, and ADMX reduced cAMP levels and increased fasting-induced Akt dephosphorylation. Unlike that observed for EDL muscles, soleus muscle proteolysis and Akt phosphorylation levels were not affected by ADMX. In isolated EDL, epinephrine reduced the basal UPS activity and suppressed overall proteolysis and atrogin-1 and MuRF1 induction following fasting. These data suggest that epinephrine released from the adrenal medulla inhibits fasting-induced protein breakdown in fast-twitch skeletal muscles, and these antiproteolytic effects on the UPS and lysosomal system are apparently mediated through a cAMP-Akt-dependent pathway, which suppresses ubiquitination and autophagy.

Effect of amino acids alone or with insulin on muscle and liver protein synthesis in adult and old rats

1993 ◽  
Vol 264 (4) ◽  
pp. E614-E620 ◽  
Author(s):  
L. Mosoni ◽  
M. L. Houlier ◽  
P. P. Mirand ◽  
G. Bayle ◽  
J. Grizard
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Male Rats ◽  
Liver Protein ◽  
Protein Mass ◽  
Age Related ◽  
Old Rats ◽  
Absolute Synthesis

This study was carried out to analyze age-related changes on amino acid and insulin effects on muscle and liver protein synthesis. Conscious male rats, aged 12 (adult) and 24 (old) mo, were infused for 90 min with either saline, amino acids, or amino acids with insulin and glucose. Protein synthesis was measured during the last 15 min of infusion (flooding dose of valine with L-[2,3,4-3H]valine). Gastrocnemius protein mass was 29% lower in old rats than in adults. However, basal muscle absolute synthesis rates were unchanged with age, and fractional synthesis rates (FSR) were increased. Amino acids significantly stimulated muscle FSR to a similar extent (18-20%) in adult (P < 0.01) and old rats (P = 0.03 when variability introduced by muscle atrophy was taken into account by a variance-covariance analysis). Insulin did not elicit any additional effect. Liver protein synthesis did not change with age or in response to infusions. We conclude that, despite an age-related loss of muscle proteins, capacity of muscle protein synthesis to be stimulated is preserved with age.

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.

scholarly journals The diurnal response of muscle and liver protein synthesis in vivo in meal-fed rats

1973 ◽  
Vol 136 (4) ◽  
pp. 935-945 ◽  
Author(s):  
P. J. Garlick ◽  
D. J. Millward ◽  
W. P. T. James
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Specific Radioactivity ◽  
Whole Body ◽  
Rat Tissues ◽  
Liver Protein ◽  
Protein Mass ◽  
Fractional Rate

1. The rate of protein synthesis in rat tissues was measured by constant intravenous infusion of [14C]tyrosine. A modification has been developed for the method of calculating the rate of protein synthesis in individual tissues from the specific radioactivity of the free and protein-bound amino acid in tissue at the end of the infusion. This technique gives greater accuracy and allows a greater choice of labelled amino acids. The specific radioactivity of free tyrosine in plasma was used to calculate the plasma tyrosine flux, an index of the rate of protein synthesis in the whole body. 2. Young male Wistar rats were allowed access to food for only 4h in every 24h. The tyrosine flux and the rate of protein synthesis in liver and muscle at different periods of time after a single feed were estimated. 3. The tyrosine flux did not alter after feeding nor even after starvation for 48h. 4. The average fractional rate of protein synthesis in muscle was 7.2%/day, i.e. the proportion of the protein mass which is replaced each day. The rate rose after eating and declined during starvation for 48h. In addition the rate of muscle protein synthesis correlated with the growth rate of the rat. 5. In liver the average fractional rate of protein synthesis was 50%/day. There was no change in the rate after eating nor after starvation for 48h. In contrast with muscle this suggests that the changes in protein mass were accompanied by changes in the rate of protein breakdown rather than synthesis.

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