title: Fatty acids regulate endothelial lipase and inflammatory markers in macrophages and in mouse aorta: a role for PPARγ.
abstract: OBJECTIVE
  Macrophage endothelial lipase (EL) is associated with increased atherosclerosis and inflammation. Because of their anti-inflammatory properties we hypothesized that n-3 fatty acids, in contrast to saturated fatty acids, would lower macrophages and arterial EL and inflammatory markers.
  
  
  RESULTS
  Murine J774 and peritoneal macrophages were incubated with eicosapentaenoic acid or palmitic acid in the presence or absence of lipopolysaccaride (LPS). LPS increased EL mRNA and protein. Palmitic acid alone or with LPS dose-dependently increased EL mRNA and protein. In contrast, eicosapentaenoic acid dose-dependently abrogated effects of LPS or palmitic acid on increasing EL expression. EL expression closely linked to peroxisome proliferator activated receptor (PPAR)γ expression. Eicosapentaenoic acid blocked rosiglitazone (a PPARγ agonist)-mediated EL activation and GW9662 (a PPARγ antagonist)-blocked palmitic acid-mediated EL stimulation. Eicosapentaenoic acid alone or with LPS blunted LPS-mediated stimulation of macrophage proinflammatory interleukin-6, interleukin-12p40, and toll-like receptor-4 mRNA and increased anti-inflammatory interleukin-10 and mannose receptor mRNA. In vivo studies in low density lipoprotein receptor knockout mice showed that high saturated fat rich diets, but not n-3 diets, increased arterial EL, PPARγ, and proinflammatory cytokine mRNA.
  
  
  CONCLUSIONS
  n-3 fatty acids, in contrast to saturated fatty acids, decrease EL in parallel with modulating pro- and anti-inflammatory markers, and these effects on EL link to PPARγ.
authors.affiliation: Institute of Human Nutrition, Columbia University, New York, NY 10032, USA.
authors.forename: Un Ju
authors.initials: UJ
authors.lastname: Jung
authors.forename: Claudia
authors.initials: C
authors.lastname: Torrejon
authors.forename: Chuchun L
authors.initials: CL
authors.lastname: Chang
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hamai
authors.forename: Tilla S
authors.initials: TS
authors.lastname: Worgall
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Deckelbaum
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D066298:In Vitro Techniques; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D047495:PPAR gamma / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D008070:Lipopolysaccharides; D047495:PPAR gamma; D011973:Receptors, LDL; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D019308:Palmitic Acid; D015118:Eicosapentaenoic Acid; D008049:Lipase; C498741:Lipg protein, mouse