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Unité de Nutrition et Métabolisme Protéique, Centre INRA de Clermont-Ferrand-Theix, 63122 Theix, France
3To whom correspondence should be addressed. E-mail: mosoni{at}clermont.inra.fr.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSAnalytical methodsRESULTSDISCUSSIONLITERATURE CITED |
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KEY WORDS: • feeding • aging • muscle • liver • intestine • rats
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSAnalytical methodsRESULTSDISCUSSIONLITERATURE CITED |
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) and humans (2
) during aging. This could lead to a slow erosion of muscle mass.
However, a high level of blood free amino acids is still able to stimulate muscle protein synthesis in old rats (3
) and elderly humans (4
). Given these results, we proposed to modulate protein feeding pattern in elderly humans (5
), i.e., without changing the total amount of protein given each day, consuming 80% of the daily protein intake during one meal (the pulse pattern) could lead to a normal stimulation of muscle protein synthesis after this meal. We postulated that for a reasonable and safe total daily intake of proteins, the pulse pattern could lead to a better efficiency of protein utilization in elderly humans. Indeed, we showed that the pulse pattern was more efficient in improving nitrogen balance than a spread pattern composed of 4 meals that equalized the daily protein intake over the feeding period (5
). This effect was not observed in young women (6
). Adaptation to the pulse pattern induced modifications of whole-body protein synthesis and degradation rates in both young and elderly women (7
), but it remains unclear what effects occurred at the tissue level. In particular, we did not measure the effect of the pulse pattern on muscle protein synthesis. In addition, splanchnic utilization of dietary leucine (8
) and phenylalanine (9
) is higher in elderly people than in young adults. The pulse pattern could also induce a higher protein gain in the splanchnic area in elderly women.
Thus, to determine which tissues or organs are the targets of the effects of the protein feeding pattern in older individuals and what are the mechanisms involved, we developed and refined a rat model with which to study liver, small intestine and muscle protein metabolism before and after meal ingestion of a pulse or a spread diet.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSAnalytical methodsRESULTSDISCUSSIONLITERATURE CITED |
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These experiments were performed in accordance with current legislation on animal experimentation in France. Sprague-Dawley mature adults (11 mo old, n = 32) and old rats (23 mo old, n = 32) were purchased from Iffa Credo (L’Arbresle, France). They were maintained in individual cages under controlled environmental conditions (temperature 21°C, humidity 55%, 12-h dark period starting at 0500 h). For 10 d, the rats were acclimated to consuming their daily food as four meals during the dark period (distributed automatically at 0500, 0800, 1100 and 1400 h), with no access to food during the light period (1700– 0500 h), but with free access to water during the 24-h period. The diet provided 16 kJ/g and 180 mg of fish protein/g. It was constituted from 24% herring meal (Lorientaise des Produits de la Pêche, Lorient, France), 65% wheat starch (Louis François, France), 4% agar agar, 3% fat (vegetable oil, Huileries de Lapalisse, France) and 4% minerals plus vitamins [see (10
) for details on diet composition]. After this adaptive period, rats of both ages were divided into two groups. In the first one, referred to as the spread group, the daily protein intake was spread equally over the 4 meals (standard protein meals). In the second group, referred to as the pulse group, 66% of daily protein intake was consumed at 0800 h during the high protein meal, whereas the remaining 33% was distributed equally among the three other low protein meals, at 0500, 1100 and 1400 h. These two diets provided the same daily amount of energy (334 kJ/d) and protein (3.6 g/d) and were fed for 21 d. Thus, only the protein feeding pattern was different, i.e., either distributed equally over the four meals (spread groups) or given mainly in one meal (pulse groups).
Practically, 3 isoenergetic diets were prepared. Diet A had the same composition as the diet of the adaptive period; 20 g of this diet (fresh food) was distributed to the spread group rats (5 g at each of the 4 meals of the dark period). Diet B had a high protein content (48%). It was prepared from 63% herring meal, 26% wheat starch, 4% agar agar, 3% fat and 4% minerals plus vitamins; 5 g (fresh food) was given to the rats of the pulse groups once a day at 0800 h, which constituted the high protein meal. Diet C had a low protein content (8% fish protein). It was prepared from 10% herring meal, 79% wheat starch, 4% agar agar, 3% fat and 4% minerals plus vitamins. This diet was supplemented with L-methionine (0.16%), L-phenylalanine (0.15%), L-tryptophan (0.03%), and threonine (0.13%); 15 g (fresh food) was distributed to the pulse group rats in three equal meals given at 0500, 1100 and 1400 h.
Measurements of tissue protein turnover rates, killing and sampling.
Tissue protein turnover measurements were performed at the end of the 21-d experiment in rats in either the postabsorptive state (PA),4 i.e., after 12 h of the light period, or in the postprandial state (PP), i.e., 2 h after the ingestion of the high protein meal (pulse groups) or 2 h after the ingestion of the standard protein meal (spread groups).
In vivo tissue protein synthesis rates were measured using the flooding dose method (11
), which reduces uncertainty over the labeling of the tracer amino acid in the precursor pool for protein synthesis. Briefly, 15 min before killing, each rat was injected with a flooding dose of L-13C valine (99 atom%, Cambridge Isotope Laboratories, Andover, MA; 150 µmol/100 g body) in the tail vein (time 0). The enrichment of the flooding dose was 50 atom% excess (APE).
General anesthesia was induced by intraperitoneal injection of pentobarbital sodium (Sanofi, Libourne, France) just before killing by exsanguination. Blood was collected in heparinized tubes and centrifuged (10 min at 3000 g). Plasma was collected and kept frozen at -20°C until further amino acid concentration determination. Liver, small intestine and gastrocnemius (plus plantaris) muscles were quickly excised and chilled on ice to stop tracer incorporation. Liver was cut into small pieces, dipped in cold saline and wiped. The small intestine was rinsed with cold trichloroacetic acid (TCA; 0.12 mol/L). All tissues were weighed and frozen in liquid nitrogen within 3–5 min after exsanguination. This extra time was not allowed for in the calculation of incorporation time. Incorporation time was measured for each rat between the time of injection and the time of exsanguination and averaged 15.57 ± 1.05 min.
In vitro protein breakdown rates were measured in epitrochlearis muscle as previously described (12
). Briefly, epitrochlearis muscles were excised within 3 min after killing and were preincubated for 30 min in a Krebs-Hensleit buffer (NaCl, 120 mmol/L; KCl, 4.8 mmol/L; NaHCO3, 25 mmol/L; CaCl2, 2.5 mmol/L; KH2PO4, 1.2 mmol/L; MgSO4, 1.2 mmol/L; pH 7.4), saturated with 95% O2/5% CO2 gas mixture, and supplemented with 5.0 mmol/L glucose, 5.0 mmol/L HEPES, 1 g/L bovine serum albumin, 0.17 mmol/L leucine, 0.20 mmol/L valine and 0.10 mmol/L isoleucine. Muscles were then transferred for 60 min into fresh medium of the same composition with the addition of [14C] L-phenylalanine for the determination of protein synthesis (data not shown). Simultaneously, protein degradation was measured from tyrosine release in the medium. Total protein breakdown was calculated as the sum of net protein breakdown and protein synthesis. At the end of the incubation, muscles were stored in 0.6 mol/L TCA solution. Both muscles and incubation media were stored at -20°C until further analysis.
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Analytical methods |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSAnalytical methodsRESULTSDISCUSSIONLITERATURE CITED |
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Tissue free amino acids were extracted using 0.6 mol/L TCA as described previously (13
). Free valine enrichment determination was then performed by gas chromatography/mass spectrometry, with a HP 5972 organic mass spectrometer quadrupole coupled to a HP 5890 GC (Helwett-Packard, Les Ulis, France). Valine was measured as the tertiary butyl-dimethylsilyl derivative under electron impact ionization. The ions m/z 288 and 289 were monitored by selective ion recording to determine the [13C]valine enrichment. Tissue protein precipitates were hydrolyzed in 6 mol/L HCl. Valine was measured as the N-acetyl-propyl-amino acid derivative. The ratio 13CO2/12CO2 was measured with a gas isotope ratio spectrometer coupled with a gas chromatograph (Isochrom II, Fisons, Manchester, UK). Tissue proteins were assayed using bicinchoninic acid (Pierce, Rockford, IL).
Epitrochlearis muscles were treated as previously described (12
). Tyrosine was determined in the incubation medium by fluorescence (14
), and protein breakdown was expressed as nmol Tyr/(mg protein · h).
After deproteinization with 0.23 mol/L sulfosalicylic acid, plasma free amino acid concentrations were measured by ion-exchange chromatography with an automatic amino acid analyzer (Biotronic LC 3000, Roucaire, Velizy, France with BTC 2410 resin) (15
).
In vivo fractional synthesis rates (FSR, %/d) were calculated according to the method described by Garlick et al. (11
): FSR = 100 x (EP - EN)/(EA x t), where t is the incorporation time (15 min), expressed in days, EP is the enrichment of protein-bound valine at the time of killing, EN is the natural enrichment of protein-bound valine, which was measured in each tissue in 5 rats fed the same fish diet and EA is the enrichment of tissue-free valine at the time of killing. EP, EN and EA were expressed in APE by reference to the enrichment of valine obtained from Sigma Chemical (St. Louis, MO). Absolute synthesis rates (ASR) were calculated by multiplying FSR by total tissue protein content (mg or g/d).
Values are given as means ± SEM or residual SD. The effects of age, and protein feeding pattern on body weight and daily food intake were analyzed during the experimental period using a three-way ANOVA with repeated measures for time. Three-way ANOVA were performed to discriminate among the effects of age (A), protein feeding pattern (P), nutritional state (N) and their interactions on tissue protein metabolism at d 21. When a main factor was not significant, another variance analysis was performed without this factor. When an interaction term was significant, mean comparisons were carried out using Student’s t test. When not specified, the level of significance used was P 
0.05. Two data points concerning liver weight were missing (one in old spread PA group and one in adult pulse PP group). Consequently, only 7 observations (instead of 8 in the other groups) were used in the statistical analysis of liver weight, protein mass and ASR in those 2 groups. StatView program (version 4.5; Abacus Concepts, Berkley, CA) was used for the statistical analyses.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSAnalytical methodsRESULTSDISCUSSIONLITERATURE CITED |
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The mean daily food consumption was slightly, but significantly lower in old rats than in adult rats (16.7 ± 0.3 and 17.8 ± 0.1 g of dried food, respectively). However, protein feeding pattern was similar at both ages, i.e., adult rats consumed 25.3 ± 0.2% of daily intake (4.46 ± 0.03 g of dry matter) and old rats consumed 25.1 ± 0.3% of daily intake (4.22 ± 0.06 g) during the second meal (0800). The protein feeding pattern had no effect on total daily food intake; dry matter intake was 17.1 ± 0.2 and 17.3 ± 0.2 g for the rats fed the spread and pulse diets, respectively. Similar amounts of food were consumed at each of the 4 meals whatever the group (spread or pulse); the mean intake during the second meal was 4.35 ± 0.06 and 4.32 ± 0.05 g of dry matter for the rats fed the pulse (high-protein meal) and spread (standard-protein meal) diet, respectively (thus protein intake was 2.09 ± 0.03 and 0.78 ± 0.01g for the pulse and spread group, respectively, for this meal).
Body weights were not different between adult and old rats, at the beginning (666 ± 12 g and 698 ± 17 g for adult and old rats, respectively) or at the end of the experimental period (676 ± 10 g and 682 ± 15 g for adult and old rats, respectively). The protein feeding pattern had no effect on body weight (682 ± 12 and 676 ± 14 g for the rats fed for 21 d with the spread and the pulse diets, respectively).
Table 1
describes the effects of age, protein feeding pattern and nutritional state, and their interactions on muscle weight, protein mass and protein turnover. Gastrocnemius weights were significantly lower in old rats than in adult rats (2.25 ± 0.09 g and 3.51 ± 0.05 g, respectively). Protein mass was also lower in old rats than in adult rats (400 ± 18 mg and 661 ± 14 mg, respectively). ASR were lower in old than in adult rats (39 ± 2 mg/d and 51 ± 2 mg/d, respectively, P < 0.05). Epitrochlearis protein breakdown was higher in old rats than in adult rats [0.73 ± 0.04 and 0.63 ± 0.02 nmol Tyr/(mg protein · h), respectively, P = 0.05].
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As expected, there was no effect of nutritional state on either gastrocnemius muscle weight (PA: 2.87 ± 0.13 g and PP: 2.88 ± 0.14 g) or protein content (PA: 522 ± 29 mg and PP: 540 ± 28 mg). By contrast, nutritional state modulated muscle protein synthesis and breakdown. In the spread groups used as reference groups, gastrocnemius ASR were significantly higher during the postprandial state than during the postabsorptive state in adult rats (59 ± 3 and 48 ± 2 mg protein synthesized/d, respectively) but not in old rats (39 ± 3 and 43 ± 4 mg protein synthesized/d, respectively). In a two-way ANOVA (not shown) with age and nutritional state as main effects, the interaction age-by-nutritional state was significant, P = 0.03. Epitrochlearis protein breakdown was lower during the postprandial state than during the postabsorptive state in adult rats but not in old rats (the age-by-nutritional state interaction was significant, P < 0.05, Fig. 1
). Thus, the regulation by feeding of both protein synthesis and breakdown was altered in muscles of old rats.
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and Fig. 2
). Gastrocnemius ASR were higher during the postprandial state than in the postabsorptive state in old rats fed the pulse diet as was observed in adult rats irrespective of diet. In old rats, when compared with the spread group, this resulted from both lower protein synthesis rates in the postabsorptive state (-35%), and higher protein synthesis rates in the postprandial state (+21%).
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Table 2
describes the effects of age, protein feeding pattern and nutritional state, and their interactions on liver weight, protein mass and protein turnover. Age did not affect liver weight (19.2 ± 0.6 and 20.2 ± 0.9 g for adult and old rats), protein content (3.8 ± 0.1 and 3.9 ± 0.1 g for adult and old rats) or ASR (2.56 ± 0.08 and 2.79 ± 0.15 g protein synthesized/d for adult and old rats). The protein feeding pattern did not affect liver weight (19.7 ± 0.8 g and 19.6 ± 0.8 g for the spread and the pulse groups, respectively) or protein content (3.89 ± 0.11 g and 3.85 ± 0.10 g for the spread and the pulse groups, respectively). Protein synthesis also was not affected by the protein feeding pattern (2.61 ± 0.10 g and 2.72 ± 0.13 g for the spread and the pulse groups, respectively).
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).
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Table 3
describes the effects of age, protein feeding pattern and nutritional state, and their interactions on small intestine weight, protein mass and protein turnover. Small intestine weight and protein content were slightly, but significantly higher in old rats than in adult rats (9.8 ± 0.3 and 8.9 ± 0.1 g for tissue weight and 1.10 ± 0.03 and 1.00 ± 0.02 g for protein content, respectively). However, there was no effect of age on ASR (0.86 ± 0.04 and 0.87 ± 0.05 g protein synthesized/d for adult and old rats, respectively), suggesting a reduction in protein degradation or in protein exportation during aging.
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Both small intestine weight (PA: 8.8 ± 0.2 g and PP: 9.9 ± 0.2 g) and protein content (PA: 0.98 ± 0.03 g and PP: 1.11 ± 0.03 g) were significantly higher during the postprandial state than during the postabsorptive state. As in liver, ASR were significantly higher in small intestine during the postprandial state than during the postabsorptive state (PP: 1.06 ± 0.03 and PA: 0.67 ± 0.02 g protein synthesized/d). In contrast to liver, this postprandial stimulation of protein synthesis occurred both in rats fed the spread pattern and those fed the pulse pattern (Fig. 3)
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Free plasma amino acid concentrations.
The plasma concentration of His, Ile, Leu, Met and Phe were not affected by age (Table 4
). Most amino acid concentrations (Ile, Leu, Met, Thr) were higher during the postprandial state than during the postabsorptive state, and this increase was similar in adult and old rats. Finally, all concentrations were higher in rats fed the pulse diet than in rats fed the spread diet. For leucine, this effect of protein feeding pattern occurred mainly during the postprandial state (protein pattern-by-nutritional state interaction significant, Table 4
).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSAnalytical methodsRESULTSDISCUSSIONLITERATURE CITED |
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). The present study was undertaken to analyze the effects of the pulse feeding pattern at the tissue level. We showed that the protein pulse pattern was indeed effective in enhancing the muscle protein synthesis response to meal ingestion in old rats, whereas there was little effect in tissues of the splanchnic area. Thus, it is likely that the positive effects of the pulse feeding pattern observed on nitrogen retention in humans occurred at the muscle level.
In the spread group, feeding increased muscle protein synthesis by 20% in adult rats but not in old rats. This is in agreement with previous data reported in tibialis anterior of rats (1
) and also in humans in quadriceps muscle (2
). However, the mechanisms involved in this age-related dysregulation of protein synthesis during the postprandial state remain unknown. Among the factors contributing to the stimulation of protein synthesis after meal ingestion, amino acid availability is likely the most important [see (16
) for a review]. Volpi et al. (9
) showed that after an oral load of amino acids (40 g), the increase in indispensable amino acid concentrations was important (leucine concentrations were 3 times higher after the amino acid load) and similar in young and elderly subjects. This allowed a stimulation of muscle protein synthesis that was not different in young and elderly subjects. This phenomenon occurred also in rats after an intravenous infusion of amino acids (3
). In addition, a high leucine concentration could be particularly important for the stimulation of protein synthesis in older organisms, i.e., Dardevet et al. (17
) showed that stimulation of in vitro protein synthesis is obtained in mature rats with a leucine concentration of 150 µmol/L, whereas a leucine concentration up to 400 µmol/L is necessary to observe the same effect in old rats. Thus, the reduced stimulation of muscle protein synthesis after feeding in older individuals could be related to a lower sensitivity to the effect of amino acids and/or leucine, and the stimulation of muscle protein synthesis obtained in old rats fed the pulse diet could be related to the greater increase in indispensable amino acid (+93 µmol) or leucine (+17%) concentrations in that group compared with the spread diet (+56 µmol for total amino acids, +2% for leucine).
Despite the positive effects of the pulse diet on muscle protein synthesis rates in old rats, it did not affect muscle mass. We noted a decrease in muscle protein mass only with aging. Muscle protein mass changes result from the balance between protein synthesis and breakdown. Direct measurements of in vivo tissue proteolysis during short periods (i.e., after meal ingestion) are technically impossible. We estimated muscle proteolysis using in vitro incubation of epitrochlearis. This allowed us to demonstrate an age-related alteration of the regulation of muscle proteolysis by meal feeding. Indeed, feeding inhibited muscle proteolysis by 20% in adult rats but not in old rats. This phenomenon could play a role in the age-related loss of muscle mass during aging. Similar results were obtained in humans at the whole-body level (18
).
In addition, this lack of postprandial inhibition was independent of the amount of protein in the meal because the pulse diet did not affect the postprandial change in epitrochlearis protein breakdown. If these measurements are representative of protein degradation in the gastrocnemius, this could explain in part the lack of a positive effect of the protein feeding pulse pattern on protein mass. It could also result from the low rate of protein synthesis in the gastrocnemius of postabsorptive pulse-fed old rats. This is consistent with the fact that postabsorptive plasma free amino acid concentrations were higher in those rats than in the old rats of the spread group and suggests that the excess of dietary amino acid was poorly used for protein synthesis, causing their plasma accumulation.
Finally, the lack of a positive effect of the pulse pattern on muscle protein mass could also result from lower protein synthesis rates in the pulse group after feeding the low protein meals. However, we also measured protein synthesis rates in the pulse groups after the third meal of the day (data not shown) and irrespective of age, there was no difference between the pulse and the spread groups (values even tended to be higher in old rats fed the pulse pattern compared with old rats fed the spread pattern).
Insulin regulates muscle proteolysis in the fed state, whereas it plays only a permissive role in the stimulation of protein synthesis (19
,20
). In elderly subjects, hyperinsulinemia is associated with high whole-body protein breakdown rates (18
,21
). An age-related resistance of protein breakdown to insulin could be involved in the default of muscle protein breakdown inhibition observed during the fed state.
In contrast to muscles, the protein content of splanchnic organs was maintained (liver) during aging, or even slightly increased (small intestine). No age-related decrease in protein synthesis was recorded. This is consistent with previous results obtained in rats (22
), and with an age-related increase of the contribution of splanchnic organs to whole-body protein turnover (23
).
Liver and small intestine protein content and synthesis rates were stimulated by feeding at both ages. As previously discussed (24
), such a stimulation of liver protein synthesis by feeding is not always detected, although liver protein degradation is thought to be clearly inhibited. No change with age in this response to feeding was recorded, whereas splanchnic extraction of leucine (8
) and phenylalanine (9
) after meal ingestion was shown to increase in elderly subjects, suggesting a higher utilization of dietary amino acids in those tissues. The responses of visceral protein synthesis to feeding were similar in old and adult rats. This does not exclude the possibility that changes in synthesis of specific proteins, which occur (fibrinogen) or not (albumin) during aging (25
), could be masked when measuring total hepatic protein synthesis.
Protein synthesis in splanchnic organs was also affected by the protein feeding pattern. In particular, a greater stimulation of liver protein synthesis after the ingestion of the high protein meal of the pulse diet than after the ingestion of standard protein meal of the spread diet was recorded. In old rats, this greater stimulation in liver did not prevent a stimulation of muscle protein synthesis. Although it is difficult to extrapolate from rats to humans, we may try to use our results obtained at the tissue level in rats to interpret our previous observations obtained only at the whole-body level in elderly women (5
,6
,18
), i.e., comparing the responses of liver and muscle protein synthesis to the pulse feeding pattern in the 2 age groups could suggest that there was also a positive effect of the pulse pattern at the muscle level in humans.
In conclusion, the present paper provides evidence that age-related impairment of muscle protein turnover involved alterations of both protein synthesis and protein breakdown after meal ingestion. These alterations could play a role in the age-related loss of muscle protein and new studies are necessary to understand the causes of these alterations.
Moreover, the use of a pulse protein feeding pattern restored the stimulation of muscle protein synthesis during feeding in old rats. These results are complementary to data obtained in elderly humans showing a positive effect of the pulse protein feeding pattern on nitrogen balance (5
). Other studies are required to optimize the conditions of the pulse protein feeding pattern (e.g., age at which the pulse protein feeding pattern should be implemented, at which meal, for how long). We anticipate that the pulse protein feeding pattern could also be useful to help the recovery of undernourished elderly patients.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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2 Supported by a grant from the firm Danone and INRA.
4 Abbreviations used: APE, atom% excess; ASR, absolute synthesis rates; FSR, fractional synthesis rates; PA, postabsorptive state; PP, postprandial state; TCA, trichloroacetic acid.
Manuscript received 10 December 2001. Initial review completed 15 January 2002. Revision accepted 21 February 2002.
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LITERATURE CITED |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSAnalytical methodsRESULTSDISCUSSIONLITERATURE CITED |
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1.
Mosoni, L., Valluy, M. C., Serrurier, B., Prugnaud, J., Obled, C., Guezennec, C. Y. & Patureau Mirand, P. (1995) Altered response of protein synthesis to nutritional state and endurance training in old rats. Am. J. Physiol. 268:E328-E335.
2.
Volpi, E., Mittendorfer, B., Rasmussen, B. B. & Wolfe, R. R. (2000) The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly. J. Clin. Endocrinol. Metab. 85:4481-4490.
3.
Mosoni, L., Houlier, M. L., Patureau Mirand, P., Bayle, G. & Grizard, J. (1993) Effect of amino acids alone or with insulin on muscle and liver protein synthesis in adult and old rats. Am. J. Physiol. 264:E614-E620.
4. Volpi, E., Ferrando, A. A., Yeckel, C. W., Tipton, K. D. & Wolfe, R. R. (1998) Exogenous amino acids stimulate net muscle protein synthesis in the elderly. J. Clin. Investig. 101:2000-2007.[Medline]
5.
Arnal, M. A., Mosoni, L., Boirie, Y., Houlier, M. L., Morin, L., Verdier, E., Ritz, P., Antoine, J. M., Prugnaud, J., Beaufrère, B. & Patureau Mirand, P. (1999) Protein pulse feeding improves protein retention in elderly women. Am. J. Clin. Nutr. 69:1202-1208.
6.
Arnal, M. A., Mosoni, L., Boirie, Y., Houlier, M. L., Morin, L., Verdier, E., Ritz, P., Antoine, J. M., Prugnaud, J., Beaufrère, B. & Patureau Mirand, P. (2000) Protein feeding pattern does not affect protein retention in young women. J. Nutr. 130:1700-1704.
7.
Arnal, M. A., Mosoni, L., Boirie, Y., Gachon, P., Genest, M., Bayle, G., Grizard, J., Arnal, M., Antoine, J. M., Beaufrère, B. & Patureau Mirand, P. (2000) Protein turnover modifications induced by the protein feeding pattern still persist after the end of dietary treatments. Am. J. Physiol. 278:E902-E909.
8.
Boirie, Y., Gachon, P. & Beaufrère, B. (1997) Splanchnic and whole-body leucine kinetics in young and elderly men. Am. J. Clin. Nutr. 65:489-495.
9.
Volpi, E., Mittendorfer, B., Wolf, S. E. & Wolfe, R. R. (1999) Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction. Am. J. Physiol. 277:E513-E520.
10.
Dardevet, D., Sornet, C., Bayle, G., Prugnaud, J., Pouyet, C. & Grizard, J. (2002) Postprandial stimulation of muscle protein synthesis in old rats was restored by a leucine-supplemented meal. J. Nutr. 132:95-100.
11. Garlick, P. J., McNurlan, M. A. & Preedy, V. R. (1980) A rapid and convenient technique for measuring the rate of protein synthesis in tissues by injection of [3H] phenylalanine. Biochem. J. 192:719-723.[Medline]
12. Dardevet, D., Sornet, C., Taillandier, D., Savary, I., Attaix, D. & Grizard, J. (1995) Sensitivity and protein turnover response to glucocorticoids are different in skeletal muscle from adult and old rats: lack of regulation of the ubiquitin-proteasome proteolytic pathway in aging. J. Clin. Investig. 96:2113-2119.
13. Savary, I., Debras, E., Dardevet, D., Sornet, C., Capitan, P., Prugnaud, J., Patureau Mirand, P. & Grizard, J. (1998) Effect of glucocorticoid excess on skeletal muscle and heart protein synthesis in adult and old rats. Br. J. Nutr. 79:297-304.[Medline]
14. Waalkes, T. P. & Udenfriend, S. (1957) A fluorometric method for the estimation of tyrosine in plasma and tissues. J. Lab. Clin. Investig. 50:733-736.
15.
Rochon, C., Tauveron, I., Dejax, C., Benoit, P., Capitan, P., Bayle, G., Prugnaud, J., Fabricio, A., Berry, C., Champredon, C., Thiéblot, P. & Grizard, J. (2000) Response of leucine metabolism to hyperinsulinemia in hypothyroid patients before and after thyroxine replacement. J. Clin. Endocrinol. Metab. 85:697-706.
16. Wolfe, R. R. & Miller, S. L. (1999) Amino acid availability controls muscle protein metabolism. Diabetes Nutr. Metab. 12:322-328.[Medline]
17.
Dardevet, D., Sornet, C., Balage, M. & Grizard, J. (2000) Stimulation of in vitro rat muscle protein synthesis by leucine decreases with age. J. Nutr. 130:2630-2635.
18. Arnal, M. A., Mosoni, L., Boirie, Y., Gachon, P., Genest, M., Bayle, G., Grizard, J., Arnal, M., Antoine, J. M., Beaufrère, B. & Patureau Mirand, P. (2000) Protein turnover modifications induced by the protein feeding pattern still persist after the end of the diets. Am. J. Physiol. 278:E902-E909.
19.
Svanberg, E., Zachrisson, H., Ohlsson, C., Iresjö, B. M. & Lundholm, K. G. (1996) Role of insulin and IGF-I in activation of muscle protein synthesis after oral feeding. Am. J. Physiol. 270:E614-E620.
20.
Sinaud, S., Balage, M., Bayle, G., Dardevet, D., Vary, T. C., Kimball, S. R., Jefferson, L. S. & Grizard, J. (1999) Diazoxide-induced insulin deficiency greatly reduced muscle protein synthesis in rats: involvement of EIF4E. Am. J. Physiol. 276:E50-E61.
21.
Boirie, Y., Gachon, P., Cordat, N., Ritz, P. & Beaufrère, B. (2001) Differential insulin sensitivities of glucose, amino acid, and albumin metabolism in elderly men and women. J. Clin. Endocrinol. Metab. 86:638-644.
22. Mosoni, L., Patureau Mirand, P., Houlier, M. L. & Arnal, M. (1993) Age-related changes in protein synthesis measured in vivo in rat liver and gastrocnemius muscle. Mech. Ageing Dev. 68:209-220.[Medline]
23. Uauy, R., Winterer, J. C., Bilmazes, C., Haverberg, L. N., Scrimshaw, N. S., Munro, H. N. & Young, V. R. (1978) The changing pattern of whole body protein metabolism in aging humans. J. Gerontol. 33:663-671.[Medline]
24. Mosoni, L., Valluy, M. C., Serrurier, B., Prugnaud, J., Obled, C., Guezennec, C. Y. & Patureau Mirand, P. (1995) Altered response of protein synthesis to nutritional state and endurance training in old rats. Am. J. Physiol. 268:E328-E335.
25.
Fu, A. & Nair, K. S. (1998) Age effect on fibrinogen and albumin synthesis in humans. Am. J. Physiol. 275:E1023-E1030.
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