title: Specialized proresolving lipid mediators in humans with the metabolic syndrome after n-3 fatty acids and aspirin.
abstract: BACKGROUND
  The metabolic syndrome (MetS) is associated with a chronic low-grade inflammatory state and may be affected by the ability to resolve inflammation, which is an active process that involves specialized proresolving lipid mediators (SPMs) derived from n-3 (ω-3) fatty acids.
  
  
  OBJECTIVE
  We compared plasma concentrations of SPMs in men and women with features of the MetS and in healthy matched control subjects in response to intakes of n-3 fatty acids and aspirin.
  
  
  METHODS
  MetS volunteers (n = 22) and healthy, matched controls (n = 21) were studied in parallel for 4 wk. Both groups took n-3 fatty acids (2.4 g/d) for 4 wk with the addition of aspirin (300 mg/d) during the last 7 d. Blood was collected at baseline and at 3 and 4 wk. Plasma SPMs were measured with the use of liquid chromatography-tandem mass spectrometry and included 18-hydroxyeicosapentaenoic acid (18-HEPE), E-series resolvins, 17-hydroxydocosahexaenoic acid (17-HDHA), D-series resolvins, 14-hydroxydocosahexaenoic acid (14-HDHA), and maresin-1.
  
  
  RESULTS
  Baseline SPMs did not differ between groups. There was an increase in the SPM precursors 18-HEPE, 17-HDHA, and 14-HDHA after n-3 fatty acid supplementation that was significantly attenuated in the MetS (P < 0.05). However, the E-series resolvins increased to a similar extent in the groups after n-3 fatty acid supplementation, and the D-series resolvins were not different from those at baseline. The addition of aspirin to n-3 fatty acids did not alter any SPMs in either group.
  
  
  CONCLUSIONS
  Volunteers with MetS had reduced plasma concentrations of the precursors of the E- and D- series resolvins as well as of 14-HDHA in response to n-3 fatty acid supplementation. However, plasma E-series resolvins were increased to a similar extent after n-3 fatty acid supplementation in both groups, and the addition of aspirin to n-3 fatty acid supplementation did not alter any of the plasma SPMs in MetS and control subjects. Additional studies in the MetS are required to determine whether SPMs affect the ability to mount an appropriate response to infection. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12610000708055.
authors.affiliation: School of Medicine & Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia; and anne.barden@uwa.edu.au.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Barden
authors.affiliation: School of Medicine & Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia; and.
authors.forename: Emilie
authors.initials: E
authors.lastname: Mas
authors.affiliation: School of Medicine & Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia; and.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Croft
authors.affiliation: Harry Perkins Institute for Medical Research, Perth, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Phillips
authors.affiliation: School of Medicine & Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia; and.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000097:blood / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D005395:Fish Oils / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D008297:Male; D024821:Metabolic Syndrome / Q000178:diet therapy / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D017698:Postmenopause; D013608:Tablets, Enteric-Coated; D014904:Western Australia; D055815:Young Adult
chemical_list: C561691:18(R)-hydroxyeicosapentaenoic acid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D013608:Tablets, Enteric-Coated; D004281:Docosahexaenoic Acids; C059528:14-hydroxydocosahexaenoic acid; C062894:17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid; D015118:Eicosapentaenoic Acid; D001241:Aspirin
keywords: aspirin; metabolic syndrome; n–3 fatty acids; protectins; resolvins