In vivo effect of ?-leucine administration on protein synthesis in mice

Funabiki, Ryuhei; Yagasaki, Kazumi; Hara, Hiroshi; Nyumura, Nobuhiro; Yoshizawa, Fumiaki; Saito, Kouichi

doi:10.1016/0955-2863(92)90014-a

Cited by 15 publications

(4 citation statements)

References 24 publications

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“…The branched-chain amino acids (BCAA) (leucine, valine, isoleucine), particularly leucine, have been demonstrated to act as a signal for muscle protein synthesis in vitro (Buse and Reid, 1975;Busquets et al, 2002;Dardevet et al, 2000;Fulks et al, 1975;Hong and Layman, 1984;Kimball et al, 1998;Kimball et al, 1999;Li and Jefferson, 1978;Mitch and Clark, 1984;Mordier et al, 2000;Tischler et al, 1982). In vivo experiments in animal models have been less consistent but confirm in vitro results that leucine acts as a signal that up-regulates muscle protein synthesis and/or down-regulates muscle protein degradation (Anthony et al, 2000;Dardevet et al, 2002;Funabiki et al, 1992;Guillet et al, 2004;Layman and Grogan, 1986;McNurlan et al, 1982;Nagasawa et al, 2002;Rieu et al, 2003). In contrast, there is limited information available on the influence of leucine alone on muscle protein synthesis in humans (Koopman et al, 2005;Nair et al, 1992;Schwenk and Haymond, 1987;Sherwin, 1978;Tessari et al, 1985).…”

Section: Muscle Massmentioning

confidence: 99%

Scientific Opinion on Dietary Reference Values for protein

Products¹

2012

EFSA Journal

359

152

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This opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) deals with the setting of Dietary Reference Values (DRVs) for protein. The Panel concludes that a Population Reference Intake (PRI) can be derived from nitrogen balance studies. Several health outcomes possibly associated with protein intake were also considered but data were found to be insufficient to establish DRVs. For healthy adults of both sexes, the average requirement (AR) is 0.66 g protein/kg body weight per day based on nitrogen balance data. Considering the 97.5 th percentile of the distribution of the requirement and assuming an efficiency of utilisation of dietary protein for maintenance of 47 %, the PRI for adults of all ages was estimated to be 0.83 g protein/kg body weight per day and is applicable both to high quality protein and to protein in mixed diets. For children from six months onwards, age-dependent requirements for growth estimated from average daily rates of protein deposition and adjusted by a protein efficiency for growth of 58 % were added to the requirement for maintenance of 0.66 g/kg body weight per day. The PRI was estimated based on the average requirement plus 1.96 SD using a combined SD for growth and maintenance. For pregnancy, an intake of 1, 9 and 28 g/d in the first, second and third trimesters, respectively, is proposed in addition to the PRI for non-pregnant women. For lactation, a protein intake of 19 g/d during the first six months, and of 13 g/d after six months, is proposed in addition to the PRI for non-lactating women. Data are insufficient to establish a Tolerable Upper Intake Level (UL) for protein. Intakes up to twice the PRI are regularly consumed from mixed diets by some physically active and healthy adults in Europe and are considered safe. © European Food Safety Authority, 2012 KEY WORDSProtein, amino acids, nitrogen balance, factorial method, efficiency of utilisation, digestibility, health outcomes. SUMMARYFollowing a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on Population Reference Intakes for the European population, including protein.Dietary proteins are the source of nitrogen and indispensable amino acids which the body requires for tissue growth and maintenance. The main pathway of amino acid metabolism is protein synthesis. In this opinion, "protein" is total nitrogen x 6.25 and protein requirements are based on nitrogen content. Protein digestion takes place in the stomach and in the small intestine. In healthy humans, the absorption and transport of amino acids is usually not limited by the availability of digestive enzymes or transport mechanisms, but some protein escapes digestion in the small intestine and is degraded in the colon through bacterial proteolysis and amino acid catabolism. By the time digesta are excreted as faeces, they consist largely of microbial protein. Therefore, when assessing protein digestibility, it is important to distinguish ...

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Section: Muscle Massmentioning

confidence: 99%

Scientific Opinion on Dietary Reference Values for protein

Products¹

2012

EFSA Journal

359

152

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“…More recently, Anthony et al (2000a) showed that orally administered leucine stimulated muscle protein synthesis by itself in vivo and this was independent of insulin. However, several authors were unable to detect an effect of leucine alone on muscle protein synthesis in post-absorptive rats or ruminants (McNurlan et al 1982;Funabiki et al 1992;Papet et al 1992). The discrepancy between in vitro and in vivo studies remains unclear.…”

Section: Regulation Of Muscle Protein Synthesismentioning

confidence: 99%

Leucine: a key amino acid in ageing-associated sarcopenia?

Dardevet

Rieu

Fafournoux

et al. 2003

NRR

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During ageing, a progressive loss of muscle mass has been well described in both man and rodents. This loss of proteins results from an imbalance between protein synthesis and degradation rates. Although some authors have shown a decrease of myofibrillar protein synthesis rates in human volunteers, this imbalance is not clearly apparent when basal rates of protein turnover are measured. A decrease in muscle protein synthesis stimulation was detected nevertheless in ageing rats during the postprandial period, suggesting that the 'meal signal' was altered during ageing. Many results now suggest that aged muscle is less sensitive to the stimulatory effect of amino acids at physiological concentrations but is still able to respond if the increase in aminoacidaemia is sufficiently large. Indeed amino acids play an important role in regulating muscle protein turnover both in vitro and in vivo. At the molecular level, amino acids modulate gene expression. Amino acid response elements have been characterised in the promoter of transcriptional factor CCAAT-enhancer binding protein homologous protein and asparagine synthetase genes. Among amino acids, leucine seems to play the major role in regulating the metabolic function. It inhibits proteolysis and stimulates muscle protein synthesis independently of insulin. Leucine has been shown to act as a real mediator by modulating specifically the activities of intracellular kinases linked to the translation of proteins such as phosphatidylinosinol 3Ј kinase and mammalian target of rapamycin-70 kDa ribosomal protein S6 (p70 S6K ) kinases. We recently demonstrated in vitro that protein synthesis of ageing rat muscles becomes resistant to the stimulatory effect of leucine in its physiological concentration range. However, when leucine concentration was increased greatly above its postprandial level, protein synthesis was stimulated normally. Moreover, we studied the effect of meal leucine supplementation on in vivo protein synthesis in adult and ageing rats. Leucine supplementation had no additional effect on muscle protein synthesis in adults but totally restored its stimulation in ageing rats. Whether chronic oral leucine supplementation would be beneficial for maintaining muscle protein mass in elderly men and women remains to be studied.

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“…While leucine's role in stimulating protein synthesis has been well established in the human (Homo sapiens; Drummond and Rasmussen, 2008), rat (Rattus norvegicus; ; Anthony et al, 2000;Crozier et al, 2005), mouse (Funabiki et al, 1992), and pig (Sus domestica; Han et al, 2008;Boutry et al, 2013), there has been little to no data related to the activating role of leucine in equine skeletal muscle. The lack of research may pose a problem as previous research using equine myogenic satellite cells has suggested distinct species differences in regards to physiological effects along with the magnitude of responses to growth factors and regulators (Greene et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Cultured equine satellite cells as a model system to assess leucine stimulated protein synthesis in horse muscle

DeBoer

Martinson

Pampusch

et al. 2018

Journal of Animal Science

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Leucine has been shown to stimulate the mammalian/mechanistic target of rapamycin (mTOR) signaling pathway which plays numerous key regulatory roles in cell growth, survival, and metabolism including protein synthesis in a number of species. However, previous work with equine satellite cells has suggested distinct species differences in regards to physiological effects and the magnitude of responses to growth factors and regulators. Because there is limited research available regarding the role of leucine in regulating equine skeletal muscle protein synthesis, the objective of this study was to evaluate the effect of leucine on the mTOR signaling pathway in cultured equine satellite. Protein synthesis was evaluated by measuring the incorporation of [3H] Phenylalanine (3HPhe) in equine satellite cell myotube cultures treated with a leucine titration ranging from 0 to 408 µM. Our results show a 1.8-fold increase (P < 0.02) in protein synthesis at levels slightly greater than those found in the general circulation, 204 and 408 µM when compared to a no leucine control (0 µM). Puromycin incorporation, a nonradioactive surface sensing of translation (SUnSET) methodology, was also measured in cells treated with leucine (LEU; 408 µM), a no-leucine control (CON), and a puromycin-negative vehicle (PURO-). These results demonstrated a 180% increase (P = 0.0056) in puromycin incorporation in LEU compared to CON cultures. To evaluate the mTOR signaling pathway, equine satellite cell myotube cultures were treated with leucine (LEU; 408 µM) or a no-leucine control (CON) in the presence or absence of rapamycin (LR and CR, respectively), an inhibitor of mTOR. The mTOR inhibitor, rapamycin, suppressed phosphorylation of mTOR (P < 0.01) and rS6 (P < 0.01) with an increase in phosphorylation of rS6 in leucine-treated cultures observed when compared to control cultures (P < 0.05). Similarly, there was a 27% increase (P < 0.005) in the hyperphosphorylated γ-form of 4E-BP1 compared to total 4E-BP1 in LEU compared to CON cultures with leucine-induced phosphorylation of 4E-BP1 completely blocked by rapamycin with a smaller decrease observed in CR compared to CON cultures. The major finding of this study was that leucine activated the mTOR translation initiation pathway and increased transcription of global proteins in cultured equine satellite cells. Use of the cell culture system with primary equine muscle cell lines provides the opportunity to distinguish the impact of leucine on muscle and protein synthesis, independent of systemic interactions.

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In vivo effect of ?-leucine administration on protein synthesis in mice

Cited by 15 publications

References 24 publications

Scientific Opinion on Dietary Reference Values for protein

Scientific Opinion on Dietary Reference Values for protein

Leucine: a key amino acid in ageing-associated sarcopenia?

Cultured equine satellite cells as a model system to assess leucine stimulated protein synthesis in horse muscle

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