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Aspartate alleviates liver injury and regulates mRNA expressions of TLR4 and NOD signaling-related genes in weaned pigs after lipopolysaccharide challenge.
J Nutr Biochem. 2014 Jun; 25(6):592-9.JN

Abstract

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.

Authors+Show Affiliations

Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China. Electronic address: yulanflower@126.com.Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.Guelph Food Research Centre, Agriculture and Agri-Food Canada, Guelph, Ontario, Canada N1G 5C9.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24767309

Citation

Leng, Weibo, et al. "Aspartate Alleviates Liver Injury and Regulates mRNA Expressions of TLR4 and NOD Signaling-related Genes in Weaned Pigs After Lipopolysaccharide Challenge." The Journal of Nutritional Biochemistry, vol. 25, no. 6, 2014, pp. 592-9.
Leng W, Liu Y, Shi H, et al. Aspartate alleviates liver injury and regulates mRNA expressions of TLR4 and NOD signaling-related genes in weaned pigs after lipopolysaccharide challenge. J Nutr Biochem. 2014;25(6):592-9.
Leng, W., Liu, Y., Shi, H., Li, S., Zhu, H., Pi, D., Hou, Y., & Gong, J. (2014). Aspartate alleviates liver injury and regulates mRNA expressions of TLR4 and NOD signaling-related genes in weaned pigs after lipopolysaccharide challenge. The Journal of Nutritional Biochemistry, 25(6), 592-9. https://doi.org/10.1016/j.jnutbio.2014.01.010
Leng W, et al. Aspartate Alleviates Liver Injury and Regulates mRNA Expressions of TLR4 and NOD Signaling-related Genes in Weaned Pigs After Lipopolysaccharide Challenge. J Nutr Biochem. 2014;25(6):592-9. PubMed PMID: 24767309.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aspartate alleviates liver injury and regulates mRNA expressions of TLR4 and NOD signaling-related genes in weaned pigs after lipopolysaccharide challenge. AU - Leng,Weibo, AU - Liu,Yulan, AU - Shi,Haifeng, AU - Li,Shuang, AU - Zhu,Huiling, AU - Pi,Dingan, AU - Hou,Yongqing, AU - Gong,Joshua, Y1 - 2014/03/06/ PY - 2013/08/28/received PY - 2013/12/15/revised PY - 2014/01/28/accepted PY - 2014/4/29/entrez PY - 2014/4/29/pubmed PY - 2014/12/24/medline KW - Aspartate KW - Lipopolysaccharide KW - Liver injury KW - Nucleotide-binding oligomerization domain protein KW - Pro-inflammatory cytokines KW - Toll-like receptor 4 KW - Weaned pigs SP - 592 EP - 9 JF - The Journal of nutritional biochemistry JO - J. Nutr. Biochem. VL - 25 IS - 6 N2 - 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. SN - 1873-4847 UR - https://www.unboundmedicine.com/medline/citation/24767309/Aspartate_alleviates_liver_injury_and_regulates_mRNA_expressions_of_TLR4_and_NOD_signaling_related_genes_in_weaned_pigs_after_lipopolysaccharide_challenge_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0955-2863(14)00038-2 DB - PRIME DP - Unbound Medicine ER -