Fish Oil Enhances Intestinal Integrity and Inhibits TLR4 and NOD2 Signaling Pathways in Weaned Pigs after LPS Challenge  

Oleh:

Liu, Yulan ; Chen, Feng

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: JN: The Journal of Nutrition vol. 142 no. 11 (Nov. 2012), page 1921-2069s.
Topik: Nutritional Immunology; Jacobi; Sheila K.

Ketersediaan

Perpustakaan FK Nomor Panggil: J42.K.2012.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Long-chain (n-3) PUFA exert beneficial effects on inflammatory bowel diseases in animal models and clinical trials. In addition, pattern recognition receptors such as toll-like receptors (TLR) and nucleotide-binding oligomerization domain proteins (NOD) play a critical role in intestinal inflammation. We hypothesized that fish oil could alleviate Escherichia coli LPS-induced intestinal injury via modulation of TLR4 and NOD signaling pathways. Twenty-four weaned piglets were used in a 2 × 2 factorial design and the main factors included a dietary treatment (5% corn oil or 5% fish oil) and immunological challenge (LPS or saline). After feeding fish oil or corn oil diets for 21 d, pigs were injected with LPS or saline. At 4 h postinjection, blood samples were collected and pigs were killed. EPA, DHA, and total (n-3) PUFA were enriched in intestinal mucosa through fish supplementation. Fish oil improved intestinal morphology, indicated by greater villus height and villus height:crypt depth ratio, and intestinal barrier function, indicated by decreased plasma diamine oxidase (DAO) activity and increased mucosal DAO activity as well as enhanced protein expression of intestinal tight junction proteins including occludin and claudin-1. Moreover, fish oil decreased intestinal TNFa and PGE2 concentrations and caspase-3 and heat shock protein 70 protein expression. Finally, fish oil downregulated the mRNA expression of intestinal TLR4 and its downstream signals myeloid differentiation factor 88, IL-1 receptor-associated kinase 1, TNFa receptor-associated factor 6, and NOD2, and its adaptor molecule, receptor-interacting serine/threonine-protein kinase 2. Fish oil decreased the protein expression of intestinal NF?B p65. These results indicate that fish oil supplementation is associated with inhibition of TLR4 and NOD2 signaling pathways and concomitant improvement of intestinal integrity under an inflammatory condition. Footnotes 1. Supported by the National Natural Science Foundation of China (31172222 and 30972109), the Program for New Century Excellent Talents in University (NCET-10-0158), the Project of Natural Science Foundation of Hubei Province (2010CDA050 and 2009CDB006), the Project of International Cooperation of Hubei Province (2011BFA008), the Hubei Provincial Department of Education (Q20111702), and the Wuhan Science and Technology Program (201171034320). 2. Author disclosures: Y. Liu, F. Chen, J. Odle, X. Lin, S. K. Jacobi, H. Zhu, Z. Wu, and Y. Hou, no conflicts of interest. 3. Supplemental Tables 1 and 2 are available from the “Online Supporting Material” link in the online posting of the article and from the same link in the online table of contents at http://jn.nutrition.org. Manuscript received: June 1, 2012. Initial review completed: July 3, 2012. Revision accepted: August

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