Please wait a minute...
投稿  |   English  | 
 
高级检索
   首页  |  最新收录  |  当期目录  |  过刊浏览  |  作者中心  |  关于期刊   开放获取  
投稿  |   English  | 
Engineering    2017, Vol. 3 Issue (5) : 760-765     https://doi.org/10.1016/J.ENG.2017.03.008
Research |
低蛋白日粮中添加亮氨酸通过雷帕霉素靶蛋白信号通路增加成年大鼠骨骼肌重量及蛋白质合成
 张博1,2,楚丽翠1,2,刘宏1,2,谢春元1,2,谯仕彦1,2,曾祥芳1,2()
1. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
2. State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing 100193, China
全文: PDF(717 KB)   HTML
导出: BibTeX | EndNote | Reference Manager | ProCite | RefWorks     支持信息
文章导读  
摘要 低蛋白日粮会减少动物组织中蛋白质沉积,影响骨骼肌增重。本文旨在研究低蛋白日粮中添加亮氨酸对成年大鼠骨骼肌重量和蛋白质合成的影响。试验选取36只平均体重为(214.4 ± 2.4)g的成年SD雄性大鼠,按体重相近原则平均分为3个处理,每个处理12个重复,每个重复1只大鼠。3个处理分别饲喂20%酪蛋白(20%C,CON)、10%酪蛋白 + 丙氨酸(10%C + Ala,R)以及10%酪蛋白 + 亮氨酸(10%C + Leu,RL)日粮,试验期为11 d,其中,10%C + Ala组和10%C + Leu组为等氮日粮组。试验第11天,所有大鼠大剂量一次性腹腔注射L-[ring-2H5]苯丙氨酸注射液,测定血清中的氨基酸含量、比目鱼肌和腓肠肌重量、蛋白质合成速率及mTOR信号通路相关分子的表达。结果表明,在3个处理中,RL组血清亮氨酸含量最高(P < 0.05),而异亮氨酸含量最低(P < 0.05);CON组的缬氨酸含量低于R和RL组(P < 0.05),但采食量、蛋白质合成速度和4EBP1的磷酸化高于R和RL组(P < 0.05),同时腹脂重量显著下降(P < 0.05)。与R组相比,RL组可以增加腓肠肌重量(P < 0.05),促进S6K1磷酸化(P < 0.05),增加骨骼肌蛋白质合成(P < 0.05)。本文结论如下,在成年大鼠长期采食低蛋白日粮的情况下,日粮中添加亮氨酸可以改善大鼠的生长性能,通过提高mTOR通路中S6K1磷酸化水平,促进大鼠骨骼肌蛋白质合成,抑制蛋白质降解。
关键词 低蛋白日粮亮氨酸生长性能肌肉重量蛋白质合成成年大鼠    
Abstract

Low protein intake causes a decrease in protein deposition in most animal tissues. The purpose of this study was to investigate whether leucine supplementation would increase the synthesis rate of protein and muscle weight in adult rats, which chronically consume only 58.8% of their protein requirements. Thirty-six male Sprague-Dawley rats were assigned to one of three dietary treatments including a 20% casein diet (CON), a 10% casein+ 0.44% alanine diet (R), and a 10% casein+ 0.87% leucine diet (RL). After a 10 d dietary treatment, plasma amino acid levels were measured after feeding, the gastrocnemius muscles and soleus muscles were harvested and weighed, and the fractional synthesis rate (FSR) and mammalian target of rapamycin (mTOR) signaling proteins in skeletal muscle were measured. Regarding the plasma amino acid level, the RL group had the highest concentration of leucine (P<0.05) and the lowest concentration of isoleucine (P<0.05) among the three groups, and the CON group had a lower concentration of valine (P<0.05) than the R and RL groups. Compared with the R and RL groups, the CON group diet significantly increased (P<0.05) feed intake, protein synthesis rate, and the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and decreased the weight of abdominal adipose. Compared with the R group, the RL group significantly increased in gastrocnemius muscle weight, protein synthesis rate, and phosphorylation of both ribosomal protein S6 kinase 1 (S6K1) and 4E-BP1. In conclusion, when protein is chronically restricted in adult rat diets, leucine supplementation moderately improves body weight gain and increases muscle protein synthesis through mTOR activation.

Keywords Low-protein diet      Leucine      Growth performance      Muscle weight      Protein synthesis      Adult rats     
基金资助: 
最新录用日期:    在线预览日期:    发布日期: 2017-11-08
服务
推荐给朋友
免费邮件订阅
RSS订阅
作者相关文章
Bo Zhang
Licui Chu
Hong Liu
Chunyuan Xie
Shiyan Qiao
Xiangfang Zeng
引用本文:   
Bo Zhang,Licui Chu,Hong Liu, et al. Leucine Supplementation in a Chronically Protein-Restricted Diet Enhances Muscle Weight and Postprandial Protein Synthesis of Skeletal Muscle by Promoting the mTOR Pathway in Adult Rats[J]. Engineering, 2017, 3(5): 760-765.
网址:  
http://engineering.org.cn/EN/10.1016/J.ENG.2017.03.008     OR     http://engineering.org.cn/EN/Y2017/V3/I5/760
CON3 R4 RL5
Ingredients (%) Corn starch 53.83 61.69 61.48
Casein 20.00 10.00 10.00
Sucrose 9.00 9.00 9.00
Soybean oil 7.00 7.00 7.00
Cellulose 5.00 5.00 5.00
Mineral premix1 3.50 3.50 3.50
Vitamin premix2 1.00 1.00 1.00
L-Lys·HCl 0.28 0.28
L-Arginine 0.12 0.12
L-Threonine 0.24 0.24
L-Tryptophan 0.02 0.09 0.09
DL-Methionine 0.40 0.70 0.70
L-Leucine 0.22 0.87
L-Isoleucine 0.18 0.18
L-Valine 0.16 0.16
L-Histidine 0.01 0.01
L-Phenylalanine 0.12 0.12
L-Alanine 0.44
Choline chloride 0.25 0.25 0.25
Analyzed nutrient levels (%) Dry matter 89.01 90.12 88.73
Crude protein 17.30 10.71 10.68
Calcium 1.30 1.32 1.30
Total phosphorus 0.37 0.35 0.35
Isoleucine 0.90 0.61 0.60
Leucine 1.74 1.07 1.73
Valine 1.17 0.73 0.75
Tab.1  Composition and nutrient levels of experimental diets (as-fed basis).
Items CON R RL SEM1 P
Performance Initial BW (g) 214.38 214.44 214.43 1.98 1.00
Final BW (g) 300.32a 284.06b 291.94ab 2.72 <0.01
Weight gain (g·d−1) 8.59a 6.96b 7.75ab 0.24 0.03
Feed intake (g·d−1) 18.22a 17.00b 16.82b 0.18 <0.01
Tissue weights Gastrocnemius muscle weight (g) 0.57ab 0.55b 0.63a 0.02 0.04
Soleus muscle weight (g) 0.18 0.19 0.21 0.02 0.53
Abdominal adipose weight (g) 6.78b 7.88a 7.94a 0.22 <0.01
Tab.2  Effects of dietary leucine supplementation in a low-protein diet on performance and relative tissue weights in adult rats.
Amino acids CON R RL SEM1 P
Essential amino acids Arginine 202.7b 303.3a 335.7a 16.6 <0.01
Histidine 92.1c 108.2b 124.2a 4.8 <0.01
Isoleucine 145.4ab 162.3a 141.6b 4.0 0.04
Leucine 203.9b 217.7b 283.4a 11.9 <0.01
Lysine 754.5b 964.8a 1089.1a 47.6 <0.01
Methionine 318.4b 476.0a 518.1a 26.0 <0.01
Phenylalanine 652.6 656.3 652.1 32.5 1.00
Threonine 728.0b 1585.7a 1515.5a 72.4 <0.01
Tryptophan 113.6b 152.7a 185.1a 10.6 <0.01
Valine 264.0b 358.6a 325.2a 13.3 <0.01
Nonessential amino acids Alanine 1516.3b 1937.7a 2099.8a 115.9 0.01
Aspartic acid 753.2 756.5 805.6 40.7 0.14
Glycine 219.0c 303.6b 351.4a 14.5 <0.01
Serine 363.4b 459.8a 507.4a 25.1 <0.01
Tyrosine 418.7 492.7 509.0 27.1 0.08
Proline 529.8 553.7 628.5 37.8 0.18
Tab.3  Effects of dietary leucine supplementation in a low-protein diet on the free amino acid concentration in the plasma of adult rats (µmol·L−1).
Fig.1  Effects of dietary leucine supplementation in a low-protein diet on the protein synthesis rate of gastrocnemius and soleus muscle in adult rats. (CON: a 20% casein diet; R: a 10% casein+ 0.44% alanine diet; RL: a 10% casein+ 0.87% leucine diet; the letters a,b,c indicate that values with different superscripts are significantly different at P<0.05.)
Fig.2  Effects of dietary leucine supplementation in a low-protein diet on the 4E-BP1 phosphorylation of skeletal muscle in adult rats. (CON: a 20% casein diet; R: a 10% casein+ 0.44% alanine diet; RL: a 10% casein+ 0.87% leucine diet; the letters a,b,c indicate that values with different superscripts are significantly different at P<0.05.)
Fig.3  Effects of dietary leucine supplementation in a low-protein diet on the S6K1 phosphorylation of skeletal muscle in adult rats. (CON: a 20% casein diet; R: a 10% casein+ 0.44% alanine diet; RL: a 10% casein+ 0.87% leucine diet; the letters a,b,c indicate that values with different superscripts are significantly different at P<0.05.)
1 Marini M, Veicsteinas A. The exercised skeletal muscle: A review. Eur J Transl Myol 2010;20(3):105–20
https://doi.org/10.4081/bam.2010.3.105
2 Manjarín R, Columbus DA, Suryawan A, Nguyen HV, Hernandez-García AD, Hoang NM, et al.. Leucine supplementation of a chronically restricted protein and energy diet enhances mTOR pathway activation but not muscle protein synthesis in neonatal pigs. Amino Acids 2016;48(1):257–67
https://doi.org/10.1007/s00726-015-2078-y
3 Gautsch TA, Anthony JC, Kimball SR, Paul GL, Layman DK, Jefferson LS. Availability of eIF4E regulates skeletal muscle protein synthesis during recovery from exercise. Am J Physiol 1998;274(2 Pt 1):C406–14.
4 Yao K, Yin Y, Chu W, Liu Z, Deng D, Li T, et al.. Dietary arginine supplementation increases mTOR signaling activity in skeletal muscle of neonatal pigs. J Nutr 2008;138(5):867–72.
5 Sugawara T, Ito Y, Nishizawa N, Nagasawa T. Supplementation with dietary leucine to a protein-deficient diet suppresses myofibrillar protein degradation in rats. J Nutr Sci Vitaminol (Tokyo) 2007;53(6):552–5
https://doi.org/10.3177/jnsv.53.552
6 Anthony JC, Reiter AK, Anthony TG, Crozier SJ, Lang CH, MacLean DA, 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. Diabetes 2002;51(4):928–36
https://doi.org/10.2337/diabetes.51.4.928
7 Li F, Yin Y, Tan B, Kong X, Wu G. Leucine nutrition in animals and humans: mTOR signaling and beyond. Amino Acids 2011;41(5):1185–93
https://doi.org/10.1007/s00726-011-0983-2
8 Columbus DA, Fiorotto ML, Davis TA. Leucine is a major regulator of muscle protein synthesis in neonates. Amino Acids 2015;47(2):259–70
https://doi.org/10.1007/s00726-014-1866-0
9 Deng D, Yao K, Chu W, Li T, Huang R, Yin Y, et al.. Impaired translation initiation activation and reduced protein synthesis in weaned piglets fed a low-protein diet. J Nutr Biochem 2009;20(7):544–52
https://doi.org/10.1016/j.jnutbio.2008.05.014
10 Anthony JC, Yoshizawa F, Anthony TG, Vary TC, Jefferson LS, Kimball SR. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. J Nutr 2000;130(10):2413–9.
11 Benevenga NJ, Calvert C, Eckhert CD, Fahey GC, Greger JL, Keen CL, et al., editors. Nutrient requirements of laboratory animals. 4th ed. Washington: National Academies Press; 1995.
12 Mao X, Zeng X, Huang Z, Wang J, Qiao S. Leptin and leucine synergistically regulate protein metabolism in C2C12 myotubes and mouse skeletal muscles. Br J Nutr 2013;110(2):256–64
https://doi.org/10.1017/S0007114512004849
13 Yin F, Liu Y, Yin Y, Kong X, Huang R, Li T, et al.. Dietary supplementation with Astragalus polysaccharide enhances ileal digestibilities and serum concentrations of amino acids in early weaned piglets. Amino Acids 2009;37(2):263–70
https://doi.org/10.1007/s00726-008-0142-6
14 Bregendahl K, Liu L, Cant JP, Bayley HS, McBride BW, Milligan LP, et al.. Fractional protein synthesis rates measured by an intraperitoneal injection of a flooding dose of L-[ring-2H5]phenylalanine in pigs. J Nutr 2004;134(10):2722–8.
15 McNurlan MA, Essén P, Thorell A, Calder AG, Anderson SE, Ljungqvist O, et al.. Response of protein synthesis in human skeletal muscle to insulin: An investigation with L-[2H5]phenylalanine. Am J Physiol 1994;267(1 Pt 1):E102–8.
16 Suryawan A, Torrazza RM, Gazzaneo MC, Orellana RA, Fiorotto ML, El-Kadi SW, et al.. Enteral leucine supplementation increases protein synthesis in skeletal and cardiac muscles and visceral tissues of neonatal pigs through mTORC1-dependent pathways. Pediatr Res 2012;71(4 Pt 1):324–31
https://doi.org/10.1038/pr.2011.79
17 Hayase K, Yokogoshi H. Effect of exercise on tissue protein synthesis in rats. Biosci Biotechnol Biochem 1992;56(10):1637–9
https://doi.org/10.1271/bbb.56.1637
18 Balage M, Dupont J, Mothe-Satney I, Tesseraud S, Mosoni L, Dardevet D. Leucine supplementation in rats induced a delay in muscle IR/PI3K signaling pathway associated with overall impaired glucose tolerance. J Nutr Biochem 2011;22(3):219–26
https://doi.org/10.1016/j.jnutbio.2010.02.001
19 Zeanandin G, Balage M, Schneider SM, Dupont J, Hébuterne X, Mothe-Satney I, et al.. Differential effect of long-term leucine supplementation on skeletal muscle and adipose tissue in old rats: An insulin signaling pathway approach. Age (Dordr) 2012;34(2):371–87
https://doi.org/10.1007/s11357-011-9246-0
20 Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu Y. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 2007;56(6):1647–54
https://doi.org/10.2337/db07-0123
21 Harper AE, Miller RH, Block KP. Branched-chain amino acid metabolism. Annu Rev Nutr 1984;4:409–54
https://doi.org/10.1146/annurev.nu.04.070184.002205
22 Dardevet D, Sornet C, Bayle G, Prugnaud J, Pouyet C, Grizard J. Postprandial stimulation of muscle protein synthesis in old rats can be restored by a leucine-supplemented meal. J Nutr 2002;132(1):95–100.
23 Rieu I, Balage M, Sornet C, Debras E, Ripes S, Rochon-Bonhomme C, et al.. Increased availability of leucine with leucine-rich whey proteins improves postprandial muscle protein synthesis in aging rats. Nutrition 2007;23(4):323–31
https://doi.org/10.1016/j.nut.2006.12.013
24 Churchward-Venne TA, Breen L, Di Donato DM, Hector AJ, Mitchell CJ, Moore DR, et al.. Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: A double-blind, randomized trial. Am J Clin Nutr 2014;99(2):276–86
https://doi.org/10.3945/ajcn.113.068775
25 Hong S, Layman DK. Effects of leucine on in vitro protein synthesis and degradation in rat skeletal muscles. J Nutr 1984;114(7):1204–12.
26 Balage M, Dardevet D. Long-term effects of leucine supplementation on body composition. Curr Opin Clin Nutr Metab Care 2010;13(3):265–70
https://doi.org/10.1097/MCO.0b013e328336f6b8
27 Kim IY, Schutzler S, Schrader A, Spencer H, Kortebein P, Deutz NE, et al.. Quantity of dietary protein intake, but not pattern of intake, affects net protein balance primarily through differences in protein synthesis in older adults. Am J Physiol Endocrinol Metab 2015;308(1):E21–8
https://doi.org/10.1152/ajpendo.00382.2014
28 Mitchell CJ, Churchward-Venne TA, Cameron-Smith D, Phillips SM. What is the relationship between the acute muscle protein synthesis response and changes in muscle mass? J Appl Physiol 2015;118(4):495–7
https://doi.org/10.1152/japplphysiol.00609.2014
29 Kimball SR, Jefferson LS. Regulation of global and specific mRNA translation by oral administration of branched-chain amino acids. Biochem Biophys Res Commun 2004;313(2):423–7
https://doi.org/10.1016/j.bbrc.2003.07.014
30 Avruch J, Lin Y, Long X, Murthy S, Ortiz-Vega S. Recent advances in the regulation of the TOR pathway by insulin and nutrients. Curr Opin Clin Nutr Metab Care 2005;8(1):67–72
https://doi.org/10.1097/00075197-200501000-00010
31 Corradetti MN, Guan KL. Upstream of the mammalian target of rapamycin: Do all roads pass through mTOR? Oncogene 2006;25(48):6347–60
https://doi.org/10.1038/sj.onc.1209885
32 Xu W, Bai K, He J, Su W, Dong L, Zhang L, et al.. Leucine improves growth performance of intrauterine growth retardation piglets by modifying gene and protein expression related to protein synthesis. Nutrition 2016;32(1):114–21
https://doi.org/10.1016/j.nut.2015.07.003
33 Kimball SR, Horetsky RL, Jefferson LS. Implication of eIF2B rather than eIF4E in the regulation of global protein synthesis by amino acids in L6 myoblasts. J Biol Chem 1998;273(47):30945–53
https://doi.org/10.1074/jbc.273.47.30945
34 Vary T. Oral leucine enhances myocardial protein synthesis in rats acutely administered ethanol. J Nutr 2009;139(8):1439–44
https://doi.org/10.3945/jn.108.098707
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
国内刊号:CN10-1244/N    国际刊号:ISSN2095-8099
版权所有 © 2015 高等教育出版社  《中国工程科学》杂志社
京ICP备11030251号-2

 Engineering