title: Changes in PTGS1 and ALOX12 Gene Expression in Peripheral Blood Mononuclear Cells Are Associated with Changes in Arachidonic Acid, Oxylipins, and Oxylipin/Fatty Acid Ratios in Response to Omega-3 Fatty Acid Supplementation.
abstract: BACKGROUND
  There is a high degree of inter-individual variability among people in response to intervention with omega-3 fatty acids (FA), which may partly explain conflicting results on the effectiveness of omega-3 FA for the treatment and prevention of chronic inflammatory diseases. In this study we sought to evaluate whether part of this inter-individual variability in response is related to the regulation of key oxylipin metabolic genes in circulating peripheral blood mononuclear cells (PBMCs).
  
  
  METHODS
  Plasma FA and oxylipin profiles from 12 healthy individuals were compared to PBMC gene expression profiles following six weeks of supplementation with fish oil, which delivered 1.9 g/d eicosapentaenoic acid (EPA) and 1.5 g/d docosahexaenoic acid (DHA). Fold changes in gene expression were measured by a quantitative polymerase chain reaction (qPCR).
  
  
  RESULTS
  Healthy individuals supplemented with omega-3 FA had differential responses in prostaglandin-endoperoxide synthase 1 (PTGS1), prostaglandin-endoperoxide synthase 2 (PTGS2), arachidonate 12-lipoxygenase (ALOX12), and interleukin 8 (IL-8) gene expression in isolated PBMCs. In those individuals for whom plasma arachidonic acid (ARA) in the phosphatidylethanolamine (PE) lipid class decreased in response to omega-3 intervention, there was a corresponding decrease in gene expression for PTGS1 and ALOX12. Several oxylipin product/FA precursor ratios (e.g. prostaglandin E2 (PGE2)/ARA for PTGS1 and 12-hydroxyeicosatetraenoic acid (12-HETE)/ARA for ALOX12) were also associated with fold change in gene expression, suggesting an association between enzyme activity and gene expression. The fold-change in PTGS1 gene expression was highly positively correlated with ALOX12 gene expression but not with PTGS2, whereas IL-8 and PTGS2 were positively correlated.
  
  
  CONCLUSIONS
  The regulation of important oxylipin metabolic genes in PBMCs varied with the extent of change in ARA concentrations in the case of PTGS1 and ALOX12 regulation. PBMC gene expression changes in response to omega-3 supplementation varied among healthy individuals, and were associated with changes in plasma FA and oxylipin composition to different degrees in different individuals.
  
  
  BACKGROUND
  clinicaltrials.gov NCT01838239.
authors.affiliation: University of Picardie Jules Verne, Amiens - Somme, France.|University of Technology in Compiègne, Compiègne-Oise, France.|Department of Nutrition, University of California Davis, Davis, CA, United States Of America.
authors.forename: Claire C
authors.initials: CC
authors.lastname: Berthelot
authors.affiliation: Department of Entomology, University of California Davis, Davis, CA, United States Of America.
authors.forename: Shizuo George
authors.initials: SG
authors.lastname: Kamita
authors.affiliation: Department of Nutrition, University of California Davis, Davis, CA, United States Of America.
authors.forename: Romina
authors.initials: R
authors.lastname: Sacchi
authors.affiliation: Department of Entomology, University of California Davis, Davis, CA, United States Of America.|Comprehensive Cancer Center, University of California Davis, Davis, CA, United States Of America.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Entomology, University of California Davis, Davis, CA, United States Of America.|Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Malin L
authors.initials: ML
authors.lastname: Nording
authors.affiliation: Department of Entomology, University of California Davis, Davis, CA, United States Of America.
authors.forename: Katrin
authors.initials: K
authors.lastname: Georgi
authors.affiliation: Department of Entomology, University of California Davis, Davis, CA, United States Of America.
authors.forename: Christine
authors.initials: C
authors.lastname: Hegedus Karbowski
authors.affiliation: Department of Food Science & Technology, University of California Davis, Davis, CA, United States Of America.|Foods for Health Institute, University of California Davis, Davis, CA, United States Of America.
authors.forename: J Bruce
authors.initials: JB
authors.lastname: German
authors.affiliation: Nephrology Division, Department of Medicine, University of California Davis, Davis, CA, United States Of America.|Medical Service, Sacramento VA Medical Center, Sacramento, CA, United States Of America.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Weiss
authors.affiliation: Scott & White Clinic, Temple, TX, United States Of America.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Hogg
authors.affiliation: Department of Entomology, University of California Davis, Davis, CA, United States Of America.|Comprehensive Cancer Center, University of California Davis, Davis, CA, United States Of America.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
authors.affiliation: Department of Nutrition, University of California Davis, Davis, CA, United States Of America.|Foods for Health Institute, University of California Davis, Davis, CA, United States Of America.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Zivkovic
mesh_terms: D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D015992:Body Mass Index; D051545:Cyclooxygenase 1 / Q000235:genetics* / Q000378:metabolism; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology*; D054883:Oxylipins / Q000378:metabolism*
chemical_list: D015525:Fatty Acids, Omega-3; D054883:Oxylipins; D016718:Arachidonic Acid; D001092:Arachidonate 12-Lipoxygenase; C476558:ALOX12 protein, human; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human