title: Stearidonic and eicosapentaenoic acids inhibit interleukin-6 expression in ob/ob mouse adipose stem cells via Toll-like receptor-2-mediated pathways.
abstract: Increased adipose tissue positively correlates with circulating inflammatory cytokines such as IL-6. We previously reported that adipose stem cells from genetically obese ob/ob mice produce significantly higher levels of IL-6 compared with other cell types such as adipocytes and macrophages within adipose tissue. We also demonstrated that (n-3) PUFA have antiinflammatory effects on adipocyte IL-6 secretion. Based on these findings, we hypothesized that EPA [20:5 (n-3)] and stearidonic acid [SDA, 18:4 (n-3)] would decrease LPS (200 μg/L)-induced IL-6 secretion and IL-6 mRNA content in the adipose stem cells. SDA (100 μmol/L) and EPA (100 μmol/L) significantly reduced LPS-induced IL-6 secretion and decreased IL-6 mRNA expression. To determine the underlying intracellular mechanisms, we tested whether LPS-induced Toll-like-receptor (TLR) 4 and TLR2 expression were modulated by these fatty acids using Western-blot analysis. EPA and SDA suppressed LPS-induced TLR2 but not TLR4 protein expression in the adipose stem cells. Furthermore, SDA and EPA significantly lowered the activation and translocation of NF-κB, a TLR2 downstream signaling target, while protein expression of extracellular signal-regulated kinases-1/2 were unaffected. Collectively, our results suggest that EPA and SDA inhibit LPS-induced IL-6 secretion and IL-6 mRNA expression in the adipose stem cells by decreasing TRL2-mediated signaling pathways.
authors.affiliation: Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Hui Wen
authors.initials: HW
authors.lastname: Hsueh
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Jay
authors.initials: J
authors.lastname: Whelan
authors.forename: Kenneth G D
authors.initials: KG
authors.lastname: Allen
authors.forename: Naima
authors.initials: N
authors.lastname: Moustaid-Moussa
authors.forename: Hyojung
authors.initials: H
authors.lastname: Kim
authors.forename: Kate J
authors.initials: KJ
authors.lastname: Claycombe
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000178:diet therapy / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015525:Fatty Acids, Omega-3; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D015118:Eicosapentaenoic Acid; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse; C062895:stearidonic acid