title: 13-hydroxy linoleic acid increases expression of the cholesterol transporters ABCA1, ABCG1 and SR-BI and stimulates apoA-I-dependent cholesterol efflux in RAW264.7 macrophages.
abstract: BACKGROUND
  Synthetic activators of peroxisome proliferator-activated receptors (PPARs) stimulate cholesterol removal from macrophages through PPAR-dependent up-regulation of liver × receptor α (LXRα) and subsequent induction of cholesterol exporters such as ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type 1 (SR-BI). The present study aimed to test the hypothesis that the hydroxylated derivative of linoleic acid (LA), 13-HODE, which is a natural PPAR agonist, has similar effects in RAW264.7 macrophages.
  
  
  METHODS
  RAW264.7 macrophages were treated without (control) or with LA or 13-HODE in the presence and absence of PPARα or PPARγ antagonists and determined protein levels of LXRα, ABCA1, ABCG1, SR-BI, PPARα and PPARγ and apolipoprotein A-I mediated lipid efflux.
  
  
  RESULTS
  Treatment of RAW264.7 cells with 13-HODE increased PPAR-transactivation activity and protein concentrations of LXRα, ABCA1, ABCG1 and SR-BI when compared to control treatment (P < 0.05). In addition, 13-HODE enhanced cholesterol concentration in the medium but decreased cellular cholesterol concentration during incubation of cells with the extracellular lipid acceptor apolipoprotein A-I (P < 0.05). Pre-treatment of cells with a selective PPARα or PPARγ antagonist completely abolished the effects of 13-HODE on cholesterol efflux and protein levels of genes investigated. In contrast to 13-HODE, LA had no effect on either of these parameters compared to control cells.
  
  
  CONCLUSIONS
  13-HODE induces cholesterol efflux from macrophages via the PPAR-LXRα-ABCA1/SR-BI-pathway.
authors: Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Heinrich-Buff-Ring 26-32, 35390 Giessen, Germany.
authors: Ines
authors: I
authors: Kämmerer
authors: Robert
authors: R
authors: Ringseis
authors: Ronald
authors: R
authors: Biemann
authors: Gaiping
authors: G
authors: Wen
authors: Klaus
authors: K
authors: Eder
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D015870:Gene Expression; D008041:Linoleic Acids / Q000494:pharmacology*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C487540:ABCG1 protein, mouse; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D015415:Biomarkers; C449302:GW 6471; D008041:Linoleic Acids; D008074:Lipoproteins; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D010080:Oxazoles; D047492:Peroxisome Proliferator-Activated Receptors; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014443:Tyrosine; C024348:13-hydroxy-9,11-octadecadienoic acid; D002784:Cholesterol