Regulation of muscle protein degradation, not synthesis, by dietary leucine in rats fed a protein-deficient diet

Sugawara, Takayuki; Ito, Yoshiaki; Nishizawa, Naoyuki; Nagasawa, Takashi

doi:10.1007/s00726-008-0180-0

Cited by 64 publications

(53 citation statements)

References 37 publications

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“…Many studies have shown that various catabolic conditions activate the ubiquitin-proteasomal pathway (30,31). We have previously shown that dietary Leu intake suppresses myofibrillar proteolysis by inhibiting the autophagiclysosomal pathway (13). Ogata et al (32) demonstrated that the ratio of LC3-II/LC3-I, a marker of the autophagic-lysosomal pathway activity, increased in a fasting duration-dependent manner.…”

Section: Discussionmentioning

confidence: 92%

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Regulation of Skeletal Muscle Protein Degradation and Synthesis by Oral Administration of Lysine in Rats

Sato

Ito

Nagasawa

2013

J Nutr Sci Vitaminol

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Summary Several catabolic diseases and unloading induce muscle mass wasting, which causes severe pathological progression in various diseases and aging. Leucine is known to attenuate muscle loss via stimulation of protein synthesis and suppression of protein degradation in skeletal muscle. The aim of this study was to investigate the effects of lysine intake on protein degradation and synthesis in skeletal muscle. Fasted rats were administered 22.8-570 mg Lys/100 g body weight and the rates of myofibrillar protein degradation were assessed for 0-6 h after Lys administration. The rates of myofibrillar protein degradation evaluated by MeHis release from the isolated muscles were markedly suppressed after administration of 114 mg Lys/100 g body weight and of 570 mg Lys/100 g body weight. LC3-II, a marker of the autophagic-lysosomal pathway, tended to decrease (p50.05, 0.08) after Lys intake (114 mg/100 g body weight). However, expression of ubiquitin ligase E3 atrogin-1 mRNA and levels of ubiquitinated proteins were not suppressed by Lys intake. Phosphorylation levels of mTOR, S6K1 and 4E-BP1 in the gastrocnemius muscle were not altered after Lys intake. These results suggest that Lys is able to suppress myofibrillar protein degradation at least partially through the autophagic-lysosomal pathway, not the ubiquitin-proteasomal pathway, whereas Lys might be unable to stimulate protein synthesis within this time frame.

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Section: Discussionmentioning

confidence: 92%

“…We have reported that supplementation with Leu under a protein-deficient diet suppresses myofibrillar protein degradation in rats (11,12). We reported that the suppression effect of Leu occurred by inhibition of the autophagic-lysosomal pathway, a proteolytic system (13). Thus, Leu also regulates muscle protein degradation.…”

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confidence: 96%

Regulation of Skeletal Muscle Protein Degradation and Synthesis by Oral Administration of Lysine in Rats

Sato

Ito

Nagasawa

2013

J Nutr Sci Vitaminol

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“…In chick skeletal muscle, leucine decreased MPB in association with decreased ubiquitin and 20S proteasome C2 subunit mRNA expression (11). However, a study in rat skeletal muscle reported no change in proteasome mRNA expression or expression of E3 ubiquitin-ligases muscle atrophy F-box (MAFbx, also known as atrogin-1) and Muscle RING Finger 1 (MuRF1), but a decrease in autophagy marker microtubule-associated protein 1 light chain 3 (LC3) B-II expression (22). Overall, verification of the effects of leucine on MPB pathways with concurrent measures of muscle protein turnover in humans is lacking.…”

Section: Introductionmentioning

confidence: 96%

Excess Leucine Intake Enhances Muscle Anabolic Signaling but Not Net Protein Anabolism in Young Men and Women

Glynn

Fry

Drummond

et al. 2010

The Journal of Nutrition

173

171

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Essential amino acids (EAA) stimulate skeletal muscle protein synthesis (MPS) in humans. Leucine may have a greater stimulatory effect on MPS than other EAA and/or decrease muscle protein breakdown (MPB). To determine the effect of 2 different leucine concentrations on muscle protein turnover and associated signaling, young men (n = 6) and women (n = 8) ingested 10 g EAA in 1 of 2 groups: composition typical of high quality proteins (CTRL; 1.8 g leucine) or increased leucine concentration (LEU; 3.5 g leucine). Participants were studied for 180 min postingestion. Fractional synthetic rate and leg phenylalanine and leucine kinetics were assessed on muscle biopsies using stable isotopic techniques. Signaling was determined by immunoblotting. Arterial leucine concentration and delivery to the leg increased in both groups and was significantly higher in LEU than in CTRL; however, transport into the muscle and intracellular availability did not differ between groups. MPS increased similarly in both groups 60 min postingestion. MPB decreased at 60 min only in LEU, but net muscle protein balance improved similarly. Components of mammalian target of rapamycin (mTOR) signaling were improved in LEU, but no changes were observed in ubiquitin-proteasome system signaling. Changes in light chain 3 and mTOR association with Unc-51-like kinase 1 indicate autophagy decreased more in LEU. We conclude that in 10 g of EAA, the leucine content typical of high quality proteins (~1.8 g) is sufficient to induce a maximal skeletal muscle protein anabolic response in young adults, but leucine may play a role in autophagy regulation.

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“…Although ingestion of essential AA has been reported to have no effect on protein breakdown (43), other studies have shown a reduction in protein degradation with branched-chain AA or leucine administration (44,48,49,53,54,66). It has been reported that branched-chain AA and leucine modulate the ubiquitin-proteasome system by regulating MAFbx/ atrogin-1 and MuRF-1 mRNA levels (4,7,38,49) and the autophagy-lysosome system through alterations in the expression of LC3II (66), although evidence to the contrary has also been reported (49). In this study, LEU infusion during CON feeding did not have any effect on the ubiquitin-proteasome system, as indicated by the lack of change in the phosphorylation of FoxO3 and in the abundance of atrogin-1 and MuRF-1.…”

Section: E628mentioning

confidence: 99%

Leucine pulses enhance skeletal muscle protein synthesis during continuous feeding in neonatal pigs

Boutry

El‐Kadi

Suryawan

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Infants unable to maintain oral feeding can be nourished by orogastric tube. We have shown that orogastric continuous feeding restricts muscle protein synthesis compared with intermittent bolus feeding in neonatal pigs. To determine whether leucine infusion can be used to enhance protein synthesis during continuous feeding, neonatal piglets received the same amount of formula enterally by orogastric tube for 25.25 h continuously (CON) with or without LEU or intermittently by bolus every 4 h (BOL). For the CON+LEU group, leucine pulses were administered parenterally (800 μmol·kg−1·h−1) every 4 h. Insulin and glucose concentrations increased after the BOL meal and were unchanged in groups fed continuously. LEU infusion during CON feeding increased plasma leucine after the leucine pulse and decreased essential amino acids compared with CON feeding. Protein synthesis in longissimus dorsi (LD), gastrocnemius, and soleus muscles, but not liver or heart, were greater in CON+LEU and BOL than in the CON group. BOL feeding increased protein synthesis in the small intestine. Muscle S6K1 and 4E-BP1 phosphorylation and active eIF4E·eIF4G complex formation were higher in CON+LEU and BOL than in CON but AMPKα, eIF2α, and eEF2 phosphorylation were unchanged. LC3-II-to-total LC3 ratio was lower in CON+LEU and BOL than in CON, but there were no differences in atrogin-1 and MuRF-1 abundance and FoxO3 phosphorylation. In conclusion, administration of leucine pulses during continuous orogastric feeding in neonates increases muscle protein synthesis by stimulating translation initiation and may reduce protein degradation via the autophagy-lysosome, but not the ubiquitin-proteasome pathway.

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Regulation of muscle protein degradation, not synthesis, by dietary leucine in rats fed a protein-deficient diet

Cited by 64 publications

References 37 publications

Regulation of Skeletal Muscle Protein Degradation and Synthesis by Oral Administration of Lysine in Rats

Regulation of Skeletal Muscle Protein Degradation and Synthesis by Oral Administration of Lysine in Rats

Excess Leucine Intake Enhances Muscle Anabolic Signaling but Not Net Protein Anabolism in Young Men and Women

Leucine pulses enhance skeletal muscle protein synthesis during continuous feeding in neonatal pigs

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