综述

亮氨酸调节哺乳动物骨骼肌蛋白质合成的研究进展

  • 毛湘冰 ,
  • 黄志清 ,
  • 陈小玲 ,
  • 余冰 ,
  • 陈代文
展开
  • 四川农业大学动物营养研究所,雅安625014
毛湘冰(1980—),男,湖南长沙人,助理研究员,博士,研究方向为动物营养与饲料科学。E-mail: acatmxb2003@163.com

收稿日期: 2010-11-26

  网络出版日期: 2011-05-16

基金资助

教育部创新团队猪抗病营养分子机制研究项目(IRTO555-5)

Leucine: Regulation on Protein Synthesis of Skeletal Muscles in Mammals

  • MAO Xiang-Bing ,
  • HUANG Zhi-Qing ,
  • CHEN Xiao-Ling ,
  • YU Bing ,
  • CHEN Dai-Wen
Expand
  • Institute of Animal Nutrition, Sichuan Agricultural University, Ya’an 625014, China

Received date: 2010-11-26

  Online published: 2011-05-16

摘要

本文综述了亮氨酸处理对哺乳动物(主要是鼠和猪)骨骼肌及其细胞蛋白质合成的影响规律,并分析讨论了这一过程中亮氨酸的作用机制。近年来,大量的体内和体外试验研究表明,长期或短期高剂量的亮氨酸处理能够刺激哺乳动物骨骼肌内蛋白质的合成,而这不仅仅是由于亮氨酸可以为骨骼肌蛋白质合成提供能量和基质,还由于其可以调节骨骼肌细胞内与蛋白质合成相关信号通路(如mTOR依赖与非依赖信号通路)的活性。

本文引用格式

毛湘冰 , 黄志清 , 陈小玲 , 余冰 , 陈代文 . 亮氨酸调节哺乳动物骨骼肌蛋白质合成的研究进展[J]. 动物营养学报, 2011 , 23(05) : 709 -714 . DOI: 10.3969/j.issn.1006-267x.2011.05.001

Abstract

The present paper reviewed the rules and mechanisms of leucine regulating protein synthesis of skeletal muscles and muscular cells in mammals, especially rodents and pigs. Recently, many in vivo and in vitro experiments showed that the protein synthesis of skeletal muscles could be increased by long- and short-term treatment of leucine. Furthermore, in this process, leucine not only acts as the substrate and the source of energy for protein synthesis, but also stimulates protein synthesis by regulating intracellular signaling pathways, which include mTOR dependent and independent pathways.[Chinese Journal of Animal Nutrition, 2011, 23(5):709 -714]

参考文献

[1]KIMBALL S R, FARRELL P A, JEFFERSON L S. Exercise effects on muscle insulin signaling and action invited review: role of insulin in translational control of protein synthesis in skeletal muscle by amino acids or exercise[J]. Journal of Applied Physiology, 2002, 93:1168-1180.

[2]SAHA A K, XU X J, LAWSON E, et al. Downregulation of AMPK accompanies leucine- and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle[J]. Diabetes, 2010, 59:2426-2434.

[3]SCHADEWALDT P, WENDEL U. Metabolism of branched-chain amino acids in maple syrup urine disease[J]. European Journal of Pediatrics, 1997, 156:S62-S66.

[4]DESANTIAGO S, TORRES N, SURYAWAN A, et al. Regulation of branched-chain amino acid metabolism in the lactating rat[J]. The Journal of Nutrition, 1998, 128:1165-1171.

[5]SHIMOMURA Y, HONDA T, SHIRAKI M, et al. Branched-chain amino acid catabolism in exercise and liver disease[J]. The Journal of Nutrition, 2006, 136:250S-253S.

[6]VARY T C, JEFFERSON L S, KIMBALL S R. Amino acid-induced stimulation of translation initiation in rat skeletal muscle[J]. American Journal of Physiology, 1999, 277:E1077-E1086.

[7]ANTHONY J C, YOSHIZAWA F, ANTHONY T G, et al. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway[J]. The Journal of Nutrition, 2000, 130:2413-2419.

[8]CROZIER S J, KIMBALL S R, EMMERT S W, et al. Oral leucine administration stimulates protein synthesis in rat skeletal muscle[J]. The Journal of Nutrition, 2005, 135:376-382.

[9]SURYAWAN A, JEYAPALAN A S, ORELLANA R A, et al. Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activation[J]. American Journal of Physiology, 2008, 295:E868-E875.

[10]NORTON L E, LAYMAN D K, BUNPO P, et al. The leucine content of a complete meal directs peak activation but not duration of skeletal muscle protein synthesis and mammalian target of rapamycin signaling in rats[J]. The Journal of Nutrition, 2009, 139:1103-1109.

[11]ESCOBAR J, FRANK J W, SURYAWAN A, et al. Leucine and  -ketoisocaproic acid,but not norleucine, stimulate skeletal muscle protein synthesis in neonatal pigs[J]. The Journal of Nutrition, 2010, 140:1418-1424.

[12]WILSON F A, SURYAWAN A, GAZZANEO M C, et al. Stimulation of muscle protein synthesis by prolonged parenteral infusion of leucine is dependent on amino acid availability in neonatal pigs[J]. The Journal of Nutrition, 2010, 140:264-270.

[13]DARDEVET D, SORNET C, BAYLE G, et al. Postprandial stimulation of muscle protein synthesis in old rats can be restored by a leucine-supplemented meal[J]. The Journal of Nutrition, 2002, 132:95-100.

[14]RIEU I, SORNET C, BAYLE G, et al. Leucine-supplemented meal feeding for ten days beneficially affects postprandial muscle protein synthesis in old rats[J]. The Journal of Nutrition, 2003, 133:1198-1205.

[15]RIEU I, BALAGE M, SORNET C, et al. Increased availability of leucine with leucine-rich whey proteins improves postprandial muscle protein synthesis in aging rats[J]. Nutrition, 2007, 23:323-331.

[16]DEBRAS E, PROD’HOMME M, RIEU I, et al. Postprandial leucine deficiency failed to alter muscle protein synthesis in growing and adult rats[J]. Nutrition, 2007, 23:267-276.

[17]LYNCH C J, HUTSON S M, PATSON B J, et al. Tissue-specific effects of chronic dietary leucine and norleucine supplementation on protein synthesis in rats[J]. American Journal of Physiology, 2002, 283:E824-E835.

[18]YIN Y, YAO K, LIU Z, et al. Supplementing L-leucine to a low-protein diet increases tissue protein synthesis in weanling pigs[J]. Amino Acids, 2010, 39:1477-1486.

[19]桑丹,孙海洲,赵存发,等. 亮氨酸对绵羊机体蛋白质合成的影响[J]. 动物营养学报,2010,22(4):951-955.

[20]GLYNN E L, FRY C S, DRUMMOD MJ, et al. Excess leucine intake enhances muscle anabolic signaling but not net protein anabolism in young men and women[J]. The Journal of Nutrition, 2010, 140:1970-1976.

[21]ANTHONY J C, REITER A K, ANTHONY T G, et al. Orally administered leucine enhances protein synthesis in skeletal muscle of diabetic rats in the absence of increases in 4E-BP1 or S6K1 phosphorylation[J]. Diabetes, 2002, 51:928-936.

[22]VENTRUCCI G, MELLO M A R, GOMES-MARCONDES M C C. Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats[J]. BMC Cancer,2007, 7:42.

[23]VARY T C. Acute oral leucine administration stimulates protein synthesis during chronic sepsis through enhanced association of eukaryotic initiation factor 4G with eukaryotic initiation factor 4E in rats[J]. The Journal of Nutrition, 2007, 137:2074-2079.

[24]KIMBALL S R, SHANTZ L M, HORETSKY R L, et al. Leucine regulates translation of specific mRNAs in L6 myoblasts through mTOR-mediated changes in availability of eIF4E and phosphorylation of ribosomal protein S6[J]. Journal of Biological Chemistry, 1999, 274:11647-11652.

[25]MORDIER S, DEVAL C, BCHET D, et al. Leucine limitation induces autophagy and activation of lysosome-dependent proteolysis in C2C12 myotubes through a mammalian target of rapamycin-independent signaling pathway[J]. Journal of Biological Chemistry, 2000, 275:29900-29906.

[26]DU M, SHEN Q, ZHU M, et al. Leucine stimulates mammalian target of rapamycin signaling in C2C12 myoblasts in part through inhibition of adenosine monophosphate-activated protein kinase[J]. Journal of Animal Science, 2007, 85:919-927.

[27]HAN B, TONG J, ZHU M, et al. Insulin-like growth factor-1(IGF-1)and leucine activate pig myogenic satellite cells through mammalian target of rapamycin(mTOR)pathway[J]. Molecular Reproduction and Development, 2008, 75:810-817.

[28]ROH C, HAN J R, TZATSOS A, et al. Nutrient-sensing mTOR-mediated pathway regulates leptin production in isolated rat adipocytes[J]. American Journal of Physiology, 2003, 284:E322-E330.

[29]LYNCH C J, GERN B, LLOYD C, et al. Leucine in food mediates some of the postprandial rise in plasma leptin concentrations[J]. American Journal of Physiology, 2006, 291:E621-E630.

[30]TOMIYA T, NISHIKAWA T, INOUE Y, et al. Leucine stimulates HGF production by hepatic stellate cells through mTOR pathway[J]. Biochemical and Biophysical Research Communications, 2007, 358:176-180. 

[31]TOMIYA T, INOUE Y, YANASE M, et al. Treatment with leucine stimulates the production of hepatocyte growth factor in vivo[J]. Biochemical and Biophysical Research Communications, 2004, 322:772-777.

[32]IJICHI C, MATSUMURA T, TSUJI T, et al. Branched-chain amino acids promote albumin synthesis in rat primary hepatocytes through the mTOR signal transduction system[J]. Biochemical and Biophysical Research Communications, 2003, 303:59-64.

[33]MAO X, ZENG X, WANG J, et al. Leucine promotes leptin receptor expression in mouse C2C12 myotubes through the mTOR pathway[J]. Molecular Biology Reports, 2010, DOI: 10.1007/s11033-010-9992-6.

[34]ICHIHARA A. BCA, HGF, and proteasomes[J]. Biochemical and Biophysical Research Communications, 1999, 266:647-651.

[35]KIM E, GORAKSHA-HICKS P, LI L, et al. Regulation of TORC1 by Rag GTPases in nutrient response[J]. Nature Cell Biology, 2008, 10:935-945.

[36]SANCAK Y, PETERSON T R, SHAUL Y D, et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1[J]. Science, 2008, 320:1496-1501.

[37]CANEDO C S, DEMEULDER B, GINION A, et al. Activation of the cardiac mTOR/p70S6K pathway by leucine requires PDK1 and correlates with PRAS40 phophorylation[J]. American Journal of Physiology, 2010, 298:E761-E769.

[38]PROUD C G. Amino acids and mTOR signalling in anabolic function[J]. Biochemical Society Transactions, 2007, 35:1187-1190.

[39]LYNCH C J. Role of leucine in the regulation of mTOR by amino acids:Revelations from structure-activity studies[J]. The Journal of Nutrition, 2001, 131:861S-865S.

[40]ANTHONY J C. Translation control of protein synthesis in skeletal muscle of post-absorptive rats following oral administration of leucine[D]. Dissertation. Pennsylvania:Pennsylvania State University,2001.

[41]O’CONNOR P M J, BUSH J A, SURYAWAN A, et al. Insulin and amino acids independently stimulate skeletal muscle protein synthesis in neonatal pigs[J]. American Journal of Physiology, 2003, 284:E110-E119.

[42]SANS M D, TASHIRO M, VOGEL N L, et al. Leucine activates pancreatic translational machinery in rats and mice through mTOR independently of CCK and insulin[J]. The Journal of Nutrition, 2006, 136:1792-1799.

[43]毛湘冰.亮氨酸与瘦素协同调节生长鼠骨骼肌蛋白质代谢的研究[D].博士学位论文.北京:中国农业大学,2010.

[44]MATSUZAKI K, KATO H, SAKAI R, et al. Transcriptomics and metabolomics of dietary leucine excess[J]. The Journal of Nutrition, 2005, 135:1571S-1575S.

[45]EDMONDS M S, BAKER D H. Amino acid excesses for young pigs:effects of excess methionine, tryptophan, threonine or leucine[J]. Journal of Animal Science, 1987, 64:1664-1671.

[46]ROPELLE E R, PAULI J R, FERNANDES M F A, et al. A central role for neuronal AMP-activated protein kinase(AMPK)and mammalian target of rapamycin(mTOR)in high-protein diet-induced weight loss[J]. Diabetes, 2008, 57:594-605.
文章导航

/