Francina J Dijk1, Miriam van Dijk2, Stéphane Walrand3, Luc J C van Loon4, Klaske van Norren5, Yvette C Luiking6. 1. Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, The Netherlands. Electronic address: francina.dijk@nutricia.com. 2. Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, The Netherlands. Electronic address: miriam.vandijk@nutricia.com. 3. Université Clermont Auvergne, INRA, UNH, Unité de Nutrition Humaine, CRNH Auvergne, F-630000 Clermont-Ferrand, France. Electronic address: stephane.walrand@inra.fr. 4. NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, The Netherlands. Electronic address: l.vanloon@maastrichtuniversity.nl. 5. Nutrition and Pharmacology, Wageningen University, The Netherlands. Electronic address: klaske.vannorren@wur.nl. 6. Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, The Netherlands; Texas A&M University, Department of Health and Kinesiology, Center for Translation Research in Aging & Longevity, College Station, United States. Electronic address: yvette.luiking@nutricia.com.
Abstract
BACKGROUND & AIMS: It has been suggested that anabolic resistance, or a blunted protein synthetic response to anabolic stimuli, contributes to the failure of muscle mass maintenance in older adults. The amino acid leucine is one of the most prominent food-related anabolic stimuli. However, data on muscle protein synthesis (MPS) after administration of a single bolus of leucine in aged populations is lacking and long-term single leucine supplementation has not been shown to increase muscle mass. This study aimed to determine the MPS response to the administration of a single bolus of leucine or to leucine combined with whey protein, in aged mice. METHODS: Overnight fasted C57/BL6RJ mice at 25-mo of age received an oral gavage with leucine or whey-protein enriched with leucine (0.75 g/kg bodyweight total leucine in both) or 0.5 mL water (fasted control). Subsequently, mice were s.c. injected with puromycin (0.04 μmol/g bw at t = 30, 45 or 60 min) and were sacrificed 30 min thereafter. Amino acid concentrations were determined in plasma and right muscle tibialis anterior (TA). Left TA was used to analyse MPS by SUnSET method and phosphorylation rate of Akt, 4E-BP1 and p70S6k by western blot. RESULTS: In aged mice, leucine administration failed to increase MPS, despite a 6-fold increase in plasma leucine and elevated muscle free leucine levels (P < 0.05). In contrast, leucine-enriched whey protein significantly stimulated MPS in aged mice at 60 min after gavage (P < 0.05). Muscle free EAA, NEAA and the phosphorylation rate of Akt, 4E-BP1 and p70S6k increased significantly (P < 0.05), only after administration of leucine-enriched whey protein. CONCLUSIONS: MPS is stimulated in aged mice by leucine-enriched whey protein but not by leucine administration only. Administration of other amino acids may be required for leucine administration to stimulate muscle protein synthesis in aged mice.
BACKGROUND & AIMS: It has been suggested that anabolic resistance, or a blunted protein synthetic response to anabolic stimuli, contributes to the failure of muscle mass maintenance in older adults. The amino acid leucine is one of the most prominent food-related anabolic stimuli. However, data on muscle protein synthesis (MPS) after administration of a single bolus of leucine in aged populations is lacking and long-term single leucine supplementation has not been shown to increase muscle mass. This study aimed to determine the MPS response to the administration of a single bolus of leucine or to leucine combined with whey protein, in aged mice. METHODS: Overnight fasted C57/BL6RJ mice at 25-mo of age received an oral gavage with leucine or whey-protein enriched with leucine (0.75 g/kg bodyweight total leucine in both) or 0.5 mL water (fasted control). Subsequently, mice were s.c. injected with puromycin (0.04 μmol/g bw at t = 30, 45 or 60 min) and were sacrificed 30 min thereafter. Amino acid concentrations were determined in plasma and right muscle tibialis anterior (TA). Left TA was used to analyse MPS by SUnSET method and phosphorylation rate of Akt, 4E-BP1 and p70S6k by western blot. RESULTS: In aged mice, leucine administration failed to increase MPS, despite a 6-fold increase in plasma leucine and elevated muscle free leucine levels (P < 0.05). In contrast, leucine-enriched whey protein significantly stimulated MPS in aged mice at 60 min after gavage (P < 0.05). Muscle free EAA, NEAA and the phosphorylation rate of Akt, 4E-BP1 and p70S6k increased significantly (P < 0.05), only after administration of leucine-enriched whey protein. CONCLUSIONS:MPS is stimulated in aged mice by leucine-enriched whey protein but not by leucine administration only. Administration of other amino acids may be required for leucine administration to stimulate muscle protein synthesis in aged mice.
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