title: Alanyl-glutamine supplementation regulates mTOR and ubiquitin proteasome proteolysis signaling pathways in piglets.
abstract: OBJECTIVE
  The aim of the present study was to investigate the effects of the alanyl-glutamine dipeptide (Ala-Gln) or the combination supplementation of free alanine and glutamine (Ala+Gln) on the mammalian target of rapamycin (mTOR) and ubiquitin-proteasome proteolysis (UPP) signaling pathways in piglets.
  
  
  METHODS
  We randomly allocated 180 piglets to three treatments with three replicates of 20 piglets each, fed with diets containing 0.62% Ala, 0.5% Ala-Gln, 0.21% Ala+0.34% Gln, respectively. The duration of the experiment was 28 d.
  
  
  RESULTS
  The results showed that Ala-Gln increased average daily gain of piglets, and decreased the ratio of feed to gain (P < 0.05). Ala-Gln supplementation increased the concentrations of Gln and glutamate and decreased the activity of glutamine synthetase in liver and skeletal muscle (P < 0.05). Ala-Gln increased the expression of glutaminase and glutamate dehydrogenate (P < 0.05). The increased phosphorylation of eIF-4 E binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1) in Ala-Gln treatment were associated with phosphorylation of the mTOR in liver and skeletal muscle. Ala+Gln did not affect the phosphorylation abundances of mTOR, 4E-BP1, or S6K1 (P > 0.05). Ala-Gln supplementation inhibited the mRNA expressions of MAFbx and MuRF1 in skeletal muscle of piglets (P < 0.05).
  
  
  CONCLUSIONS
  Taken together, Ala-Gln supplementation improved the growth performance of piglets, enhanced the metabolism of Gln, upregulated protein synthetic signaling in liver and skeletal muscle and decreased protein degradative signaling in muscle of piglets. Moreover, these effects of Ala-Gln were more effective than those of Ala+Gln.
authors.affiliation: College of Animal Science and Technology; Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing Agricultural University, Nanjing, People's Republic of China; Department of Agricultural Science and Technology, Zunyi Normal College, Zunyi, People's Republic of China.
authors.forename: Bolin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology; Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Lin
authors.affiliation: College of Animal Science and Technology; Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Changning
authors.initials: C
authors.lastname: Yu
authors.affiliation: College of Animal Science and Technology; Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Jiaolong
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology; Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology; Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Center for Animal Disease Control and Prevention of Jintan, Jintan, People's Republic of China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Yang
authors.affiliation: College of Animal Science and Technology; Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing Agricultural University, Nanjing, People's Republic of China. Electronic address: gaofeng0629@sina.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: College of Animal Science and Technology; Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000409:Alanine / Q000008:administration & dosage; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D019587:Dietary Supplements; D004151:Dipeptides / Q000008:administration & dosage*; D005969:Glutamate Dehydrogenase / Q000235:genetics; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005972:Glutaminase / Q000235:genetics; D005973:Glutamine / Q000008:administration & dosage / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D034421:Sus scrofa; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D004151:Dipeptides; D012333:RNA, Messenger; D014452:Ubiquitins; D005973:Glutamine; D018698:Glutamic Acid; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D058570:TOR Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex; D005972:Glutaminase; D005974:Glutamate-Ammonia Ligase; D000409:Alanine; C054122:alanylglutamine
keywords: Alanyl-glutamine; Glutaminolysis; Piglet; Ubiquitin-proteasome proteolysis signaling; mTOR signaling