title: Asparagine reduces the mRNA expression of muscle atrophy markers via regulating protein kinase B (Akt), AMP-activated protein kinase α, toll-like receptor 4 and nucleotide-binding oligomerisation domain protein signalling in weaning piglets after lipopolysaccharide challenge.
abstract: Pro-inflammatory cytokines are critical in mechanisms of muscle atrophy. In addition, asparagine (Asn) is necessary for protein synthesis in mammalian cells. We hypothesised that Asn could attenuate lipopolysaccharide (LPS)-induced muscle atrophy in a piglet model. Piglets were allotted to four treatments (non-challenged control, LPS-challenged control, LPS+0·5 % Asn and LPS+1·0 % Asn). On day 21, the piglets were injected with LPS or saline. At 4 h post injection, piglet blood and muscle samples were collected. Asn increased protein and RNA content in muscles, and decreased mRNA expression of muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1). However, Asn had no effect on the protein abundance of MAFbx and MuRF1. In addition, Asn decreased muscle AMP-activated protein kinase (AMPK) α phosphorylation, but increased muscle protein kinase B (Akt) and Forkhead Box O (FOXO) 1 phosphorylation. Moreover, Asn decreased the concentrations of TNF-α, cortisol and glucagon in plasma, and TNF-α mRNA expression in muscles. Finally, Asn decreased mRNA abundance of muscle toll-like receptor (TLR) 4 and nucleotide-binding oligomerisation domain protein (NOD) signalling-related genes, and regulated their negative regulators. The beneficial effects of Asn on muscle atrophy may be associated with the following: (1) inhibiting muscle protein degradation via activating Akt and inactivating AMPKα and FOXO1; and (2) decreasing the expression of muscle pro-inflammatory cytokines via inhibiting TLR4 and NOD signalling pathways by modulation of their negative regulators.
authors: 1Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety,Wuhan Polytechnic University,Wuhan 430023,People's Republic of China.
authors: Xiuying
authors: X
authors: Wang
authors: 1Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety,Wuhan Polytechnic University,Wuhan 430023,People's Republic of China.
authors: Yulan
authors: Y
authors: Liu
authors: 1Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety,Wuhan Polytechnic University,Wuhan 430023,People's Republic of China.
authors: Shuhui
authors: S
authors: Wang
authors: 1Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety,Wuhan Polytechnic University,Wuhan 430023,People's Republic of China.
authors: Dingan
authors: D
authors: Pi
authors: 1Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety,Wuhan Polytechnic University,Wuhan 430023,People's Republic of China.
authors: Weibo
authors: W
authors: Leng
authors: 1Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety,Wuhan Polytechnic University,Wuhan 430023,People's Republic of China.
authors: Huiling
authors: H
authors: Zhu
authors: 1Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety,Wuhan Polytechnic University,Wuhan 430023,People's Republic of China.
authors: Jing
authors: J
authors: Zhang
authors: 1Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety,Wuhan Polytechnic University,Wuhan 430023,People's Republic of China.
authors: Haifeng
authors: H
authors: Shi
authors: 1Hubei Key Laboratory of Animal Nutrition and Feed Science,Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety,Wuhan Polytechnic University,Wuhan 430023,People's Republic of China.
authors: Shuang
authors: S
authors: Li
authors: 2Laboratory of Developmental Nutrition,Department of Animal Science,North Carolina State University,Raleigh,NC 27695,USA.
authors: Xi
authors: X
authors: Lin
authors: 2Laboratory of Developmental Nutrition,Department of Animal Science,North Carolina State University,Raleigh,NC 27695,USA.
authors: Jack
authors: J
authors: Odle
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001216:Asparagine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D044783:F-Box Proteins / Q000032:analysis / Q000235:genetics; D000071161:Forkhead Box Protein O1 / Q000037:antagonists & inhibitors; D015870:Gene Expression / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry; D009133:Muscular Atrophy / Q000139:chemically induced / Q000235:genetics*; D053472:Nod Signaling Adaptor Proteins / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D063150:Polycomb Repressive Complex 1 / Q000032:analysis / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D034421:Sus scrofa; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014886:Weaning
chemical_list: D044783:F-Box Proteins; D000071161:Forkhead Box Protein O1; D008070:Lipopolysaccharides; D009124:Muscle Proteins; D053472:Nod Signaling Adaptor Proteins; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D001216:Asparagine; D063150:Polycomb Repressive Complex 1; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases
keywords:  AMPK AMP-activated protein kinase;  Akt protein kinase B;  Asn asparagine;  CENTB1 centaurin β1;  CONTR non-challenged control;  FOXO Forkhead Box O;  GAPDH glyceraldehyde 3-phosphate dehydrogenase;  LD 
                    longissimus dorsi
                 ;  LPS lipopolysaccharide;  MAFbx muscle atrophy F-box;  MuRF1 muscle RING finger 1;  MyD88 myeloid differentiation factor 88;  NOD nucleotide-binding oligomerisation domain protein;  RP105 radioprotective 105;  SOCS1 suppressor of cytokine signalling 1;  TLR toll-like receptor;  Tollip toll-interacting protein;  pAMPKα
                  phosphorylated AMPKα
                 ;  pAkt phosphorylated Akt;  tAMPKα
                  total AMPKα
                 ;  tAkt total Akt;  tFOXO1 total FOXO 1; Asparagine; Lipopolysaccharides; Muscle atrophy; Pro-inflammatory cytokines