title: n-3 PUFA attenuate lipopolysaccharide-induced down-regulation of toll-like receptor 4 expression in porcine adipose tissue but does not alter the expression of other immune modulators.
abstract: The objective of this study was to test the hypothesis that the inflammatory response to lipopolysaccharide (LPS) in vivo is accompanied by down-regulation of toll-like receptor (TLR) 4 in adipose tissue, and a source of protected n-3 polyunsaturated fatty acid (PUFA) attenuates this response. Seventy-two castrated male pigs were individually fed either a control (CONT) diet, or the CONT diet containing 1.87% (LF) or 7.50% (HF) protected n-3 PUFA on a weight basis for 7 weeks. Adipose and muscle tissue biopsy samples were taken at Weeks 1, 2, 3, 4 and 7 to assess gene expression and/or confirm tissue enrichment with eicosapentaenoic acid and docosahexaenoic acid and reflected the n-3 PUFA contained in the diet. The LPS challenge was performed at week 7 and consisted of sequential injections of 10 and 2.5 mug LPS per kilogram of body weight 23 h apart. The LPS challenge resulted in a marked down-regulation (P=.004) of TLR4 at the protein level in the adipose tissue of challenged vs. control pigs, but LF and HF clearly blocked this response at the mRNA level. Although LF and HF also attenuated (P<.001) the LPS-induced acute febrile response and lowered (P<.002) serum concentrations of tumour necrosis factor alpha. Cyclooxygenase 2 and 12-lipoxygenase were readily expressed in porcine adipose tissue, but there was no effect of LF, HF or LPS on expression levels of these inflammatory mediators, or that of TNF and interleukin 6, at the conclusion of the challenge period. These findings indicate that adipose tissue responds to LPS administration in vivo by reducing TLR4 mRNA and protein abundance and that the anti-inflammatory effects of n-3 PUFA do not include down-regulation of TLR4 in adipose tissue.
authors: Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011, USA.
authors: Nicholas K
authors: NK
authors: Gabler
authors: Joel D
authors: JD
authors: Spencer
authors: Doug M
authors: DM
authors: Webel
authors: Michael E
authors: ME
authors: Spurlock
mesh_terms: D055372:AMP-Activated Protein Kinases; D000273:Adipose Tissue / Q000737:chemistry*; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D004032:Diet; D015536:Down-Regulation / Q000187:drug effects*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D005334:Fever; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009097:Multienzyme Complexes / Q000235:genetics; D018482:Muscle, Skeletal / Q000737:chemistry; D009919:Orchiectomy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015525:Fatty Acids, Omega-3; D008070:Lipopolysaccharides; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D001092:Arachidonate 12-Lipoxygenase; D051546:Cyclooxygenase 2; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases