title: Aspartate attenuates intestinal injury and inhibits TLR4 and NODs/NF-κB and p38 signaling in weaned pigs after LPS challenge.
abstract: OBJECTIVE
  This study was conducted to investigate whether aspartate (Asp) could alleviate Escherichia coli lipopolysaccharide (LPS)-induced intestinal injury by modulating intestine inflammatory response.
  
  
  METHODS
  Twenty-four weaned piglets were divided into four treatments: (1) non-challenged control; (2) LPS-challenged control; (3) LPS + 0.5 % Asp; and (4) LPS + 1.0 % Asp. After feeding with control, 0.5 or 1.0 % Asp-supplemented diets for 21 days, pigs were injected intraperitoneally with saline or LPS. At 4 h postinjection, blood and intestine samples were obtained.
  
  
  RESULTS
  Asp supplementation to LPS-challenged pigs improved intestinal morphology, indicated by higher jejunal and ileal villus height/crypt depth ratio and lower ileal crypt depth linearly or quadratically. Asp also improved intestinal barrier function, indicated by increased jejunal and ileal diamine oxidase activities as well as enhanced protein expression of jejunal claudin-1 linearly or quadratically. In addition, Asp decreased plasma, jejunal and ileal tumor necrosis factor-α concentration and ileal caspase-3 protein expression linearly and quadratically. Moreover, Asp down-regulated the mRNA expression of toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain protein (NOD) signaling-related genes, nuclear factor-κB (NF-κB) p65 and p38, decreased phosphorylation of jejunal p38, and increased phosphorylation of ileal extracellular signal-related kinase 1/2 linearly or quadratically. Finally, Asp increased mRNA expressions of TLR4 and NOD signaling negative regulators including radioprotective 105, suppressor of cytokine signaling 1, toll-interacting protein, Erbb2 interacting protein and centaurin β1 linearly or quadratically.
  
  
  CONCLUSIONS
  These results indicate that Asp supplementation is associated with inhibition of TLR4 and NODs/NF-κB and p38 signaling pathways and concomitant improvement of intestinal integrity under an inflammatory condition.
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China. yulanflower@126.com.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Shi
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Dingan
authors.initials: D
authors.lastname: Pi
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Weibo
authors.initials: W
authors.lastname: Leng
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology*; D053148:Caspase 3 / Q000097:blood; D015536:Down-Regulation; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053472:Nod Signaling Adaptor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014886:Weaning; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D053472:Nod Signaling Adaptor Proteins; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D001224:Aspartic Acid; D006631:Amine Oxidase (Copper-Containing); D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: Aspartate; Inflammatory response; Intestine injury; Lipopolysaccharide; Weaned piglets