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| 1 | Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway显示文摘Neonatal growth is characterized by a high protein synthesis rate that is largely due to an enhanced sensitivity to the postprandial rise in insulin and amino acids, especially leucine. The mechanism of leucine's action in vivo is not well understood. In this study, we investigated the effect of leucine infusion on protein synthesis in skeletal muscle and liver of neonatal pigs. To evaluate the mode of action of leucine, we used rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) complex-1 (mTORC1). Overnight-fasted 7-day-old piglets were treated with rapamycin for 1 hour and then infused with leucine (400 μmol·kg -1 ·h -1 ) for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) phosphorylation in gastrocnemius and masseter muscles (P < 0.05), but not in the liver. The leucine-induced stimulation of protein synthesis and S6K1 and 4E-BP1 phosphorylation were completely blocked by rapamycin, suggesting that leucine action is by an mTORC1-dependent mechanism. Neither leucine nor rapamycin had any effect on the activation of the upstream mTORC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of eIF2a and elongation factor 2 was not affected by leucine or rapamycin, indicating that these two pathways are not limiting steps of leucine-induced protein synthesis. These results suggest that leucine stimulates muscle protein synthesis in neonatal pigs by inducing the activation of mTORC1 and its downstream pathway leading to mRNA translation. | Agus Suryawan Hanh V Nguyen Rosemarie D Almonaci Teresa A Davis | 2012 | Journal of Animal Science and Biotechnology2012，3，1： | 9 |
| 2 | Regulation of protein degradation pathways by amino acids and insulin in skeletal muscle of neonatal pigs显示文摘Background:The rapid gain in lean mass in neonates requires greater rates of protein synthesis than degradation.We previously delineated the molecular mechanisms by which insulin and amino acids,especially leucine,modulate skeletal muscle protein synthesis and how this changes with development.In the current study,we identified mechanisms involved in protein degradation regulation.In experiment 1,6- and 26-d-old pigs were studied during 1) euinsulinemic-euglycemic-euaminoacidemic,2) euinsulinemic-euglycemic-hyperaminoacidemic,and 3)hyperinsulinemic-euglycemic-euaminoacidemic clamps for 2 h.In experiment 2,5-d-old pigs were studied during1) euinsulinemic-euglycemic-euaminoacidemic-euleucinemic,2) euinsulinemic-euglycemic-hypoaminoacidemichyperleucinemic,and 3) euinsulinemic-euglycemic-euaminoacidemic-hyperleucinemic clamps for 24 h.We determined in muscle indices of ubiquitin-proteasome,i.e.,atrogin-1(MAFbx) and muscle RING-finger protein-1(MuRFI) and autophagy-lysosome systems,i.e.,unc51-like kinase 1(UKL1),microtubule-associated protein light chain 3(LC3),and lysosomal-associated membrane protein 2(Lamp-2).For comparison,we measured ribosomal protein S6(rpS6) and eukaryotic initiation factor 4E(elF4E) activation,components of translation initiation.Results:Abundance of atrogin-1,but not MuRFI,was greater in 26- than 6-d-old pigs and was not affected by insulin,amino acids,or leucine.Abundance of ULK1 and LC3 was higher in younger pigs and not affected by treatment.The LC3-II/LC3-I ratio was reduced and ULK1 phosphorylation increased by insulin,amino acids,and leucine.These responses were more profound in younger pigs.Abundance of Lamp-2 was not affected by treatment or development.Abundance of elF4 E,but not rpS6,was higher in 6- than 26-d-old-pigs but unaffected by treatment.Phosphorylation of elF4 E was not affected by treatment,however,insulin,amino acids,and leucine stimulated rpS6 phosphorylation,and the responses decreased with development.Conclusions:The rapid growth of neonatal muscle is in part due to the positive balance between the activation of protein synthesis and degradation signaling.Insulin,amino acids,and,particularly,leucine,act as signals to modulate muscle protein synthesis and degradation in neonates. | Agus Suryawan Teresa A Davis | 2014 | Journal of Animal Science and Biotechnology2014，5，3： | 4 |
| 3 | Physiological rise in plasma leucine stimulates muscle protein synthesis in neonatal pigs by enhancing translation initiation factor activation显示文摘 | Escobar J Frank J W Suryawan A | 2005 | American Journal of PhysiologFEndocrinology and Metabolism2005，288，： | 1 |
| 4 | Regulation of cardiac and skeletal muscle protein synthesis by individual branched chain amino acids in neonatal pigs显示文摘 | Escobar J Frank J W Suryawan A | 2006 | American Journal of PhysiologFEndocrinology and Metabolism2006，290，： | 1 |
| 5 | Effect of antiserum to rat adipocytes on growth and body compositon of the rat显示文摘 | Hu C Y Suryawan A Killefer J | 1992 | Comp Biochem Physuil1992，101，： | 1 |
| 6 | Car- diac and skeletal muscle protein synthesis and activa- tion of translation initiation factors are stimulated by leucine,but not isoleucine or valine, in neonatal pigs 显示文摘 | ESCOBAR J FRANK J SURYAWAN A | 2005 | Journal of dairy science2005，88，： | 1 |
| 7 | Enteral leucine supplementation increases protein synthesis in skeletal and cardiac muscles and visceral tissues of neonatal pigs through mTORC 1-dependent pathways 显示文摘 | Suryawan A Torrazza RM Gazzaneo MC | 2012 | Pediatr Res2012，71，41： | 1 |
| 8 | Effect of antiserum to rat adipocytes on growth and body composition of the rat显示文摘 | HU C Y SURYAWAN A KILLEFER J | 1992 | Comp Biochem and Physiol Part A Physiol1992，101，4： | 1 |
| 9 | Triennial growth symposium :leucine acts as a nutrient signal to stimulate protein synthesis in neo- natal pigs 显示文摘 | SURYAWAN A ORELLANA R A FIOROTTO M L | 2011 | Journal of Animal Science2011，89，7： | 1 |
| 10 | Triennial growth symposium : leucine acts as anutrient signal to stimulate protein synthesis in neo-natal pigs 显示文摘 | SURYAWAN A ORELLANA R A FIOROTTO ML | 2011 | Journal of Animal Science2011，89，7： | 1 |
| 11 | Dietary protein and lactose increase translation initiation factor activation and tissue protein synthesis in neonatal pigs显示文摘 | FRANK J W ESCOBAR J SURYAWAN A | 2006 | American Journal of Physiology:Endocrinology and Metabolism2006，290，2： | 1 |
| 12 | Leucine supplementation of a low-protein meal increases skeletal muscle and visceral tissue protein synthesis in neonatal pigs by stimulating mTORdependent translation initiation显示文摘 | TORRAZZA R M SURYAWAN A GAZZANEO M C | 2010 | The Journal of Nutrition2010，140，12： | 1 |
| 13 | Development aggra- vates the severity of skeletal muscle catabolism induced by en- dotoxemia in neonatal pigs显示文摘 | Orellana R A Suryawan A Wilson F A | 2012 | Am J Physiol Regul Integr Comp Physiol2012，302，6： | 1 |
| 14 | Amino acid availability and age affect the leucine stimulation of protein synthesis and eIF4F formation in muscle显示文摘 | ESCOBAR J FRANK J W SURYAWAN A | 2007 | American Journal of Physiology:Endocrinology and Metabolism2007，293，6： | 1 |
| 15 | Regulation of branched-chain amino acid metabo- lism in the lactating rate显示文摘 | DE SANTIAGO S TORRES N SURYAWAN A | 1998 | The Journal of Nutrition1998，128，7： | 1 |
| 16 | Branched-chain amino acid catabolism: unique segregation of pathway enzymes in organ systems and peripheral nerves显示文摘 | SWEATT A J WOOD M SURYAWAN A | 2004 | The American Journal of Physiology: Endocrinology and Metabolism2004，286，： | 1 |
| 17 | Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activation显示文摘 | SURYAWAN A JEYAPALAN A S ORELLANA R A | 2008 | American Journal of Physiology-Endocrinology and Metabolism2008，295，4： | 1 |
| 18 | Modulation of muscle protein synthesis by insulin is maintained during neonatal endotoxemia显示文摘 | Orellana R A O'Connor P M J Bush J A Suryawan A Thivierge M C Nguyen H V Fiorotto M L Davis T A | 2006 | Am J Physiol Endocrinol Metabol2006，，： | 1 |
| 19 | Regulation of translation initiation by insulin and amino acids in skeletal muscle of neonatal pigs显示文摘 | O' CONNOR P M KIMBALL S R SURYAWAN A | 2003 | American Journal of Physiology:Endocrinology Metabolism2003，285，1： | 1 |
| 20 | Activation by insulin and amino acids of signaling components leading to translation initiation in skeletal muscle of neonatal pigs is developmentally regulated显示文摘 | SURYAWAN A ORELLANA R A NGUYEN H V | 2007 | American Journal of Physiology:Endocrinology and Metabolism2007，293，6： | 1 |
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