Aspartate alleviates liver injury and regulates mRNA expressions of TLR4 and NOD signaling-related genes in weaned pigs after lipopolysaccharide challenge.
Pro-inflammatory cytokines play a critical role in many models of liver injury. In addition, aspartate (Asp) plays an important role in many biological and physiological processes including liver physiology. We hypothesized that Asp could alleviate lipopolysaccharide (LPS)-induced liver injury. Forty-eight weanling pigs were assigned to four treatments including: (1) non-challenged control; (2) LPS challenged control; (3) LPS+0.5% Asp; (4) LPS+1.0% Asp. After 20-d feeding with control (0% Asp), 0.5% or 1.0% Asp supplemented diets, pigs were injected with saline or LPS. At 4 (early phase) and 24 h (late phase) post-injection, blood and liver samples were obtained. Asp attenuated liver injury indicated by reduced serum aspartate aminotransferase activity and increased ratio of serum alanine aminotransferase and aspartate aminotransferase at 24 h, and less severe histological liver damage induced by LPS challenge at 4 or 24 h. In addition, Asp supplementation to LPS challenged pigs decreased mRNA expressions of tumor necrosis factor (TNF)-α and cyclooxygenase-2 linearly and quadratically at 4 h, and increased mRNA expressions of these pro-inflammatory mediators linearly and quadratically at 24 h. Finally, Asp decreased mRNA expression of toll-like receptor 4 (TLR4) signaling related genes (TLR4, myeloid differentiation factor 88, IL-1 receptor-associated kinase 1, TNF-α receptor-associated factor (6), nucleotide-binding oligomerization domain protein (NOD) signaling related genes (NOD1, NOD2 and receptor-interacting serine/threonine-protein kinase 2) and nuclear factor-κB p65 linearly or quadratically at 4 h. However, Asp increased mRNA expressions of these signaling molecules linearly or quadratically at 24 h. These results indicate that, at early and late phases of LPS challenge, Asp exerts opposite regulatory effects on mRNA expression of hepatic pro-inflammatory cytokines and TLR4 and NOD signalling related genes, and improves liver integrity.
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.
Weibo
W
Leng
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China. Electronic address: yulanflower@126.com.
Yulan
Y
Liu
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.
Haifeng
H
Shi
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.
Shuang
S
Li
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.
Huiling
H
Zhu
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.
Dingan
D
Pi
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.
Yongqing
Y
Hou
Guelph Food Research Centre, Agriculture and Agri-Food Canada, Guelph, Ontario, Canada N1G 5C9.
Joshua
J
Gong
D000818:Animals; D001224:Aspartic Acid / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002681:China; D003433:Crosses, Genetic; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000097:blood; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D053472:Nod Signaling Adaptor Proteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D034421:Sus scrofa; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014886:Weaning
D015415:Biomarkers; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D053472:Nod Signaling Adaptor Proteins; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D001224:Aspartic Acid
Aspartate; Lipopolysaccharide; Liver injury; Nucleotide-binding oligomerization domain protein; Pro-inflammatory cytokines; Toll-like receptor 4; Weaned pigs