title: Effects of the omega-6:omega-3 fatty acid ratio of fat emulsions on the fatty acid composition in cell membranes and the anti-inflammatory action.
abstract: BACKGROUND
  This study investigated the effects of parenterally administered fish oil (FO) on the fatty acid composition in rats to determine the optimal omega-6:omega-3 polyunsaturated fatty acid (PUFA) ratio of fat emulsions to achieve an anti-inflammatory effect.
  
  
  METHODS
  Male Sprague-Dawley rats were infused a parenteral nutrition (PN) solution containing fat emulsions with different omega-6:omega-3 PUFA ratios. The fatty acid content of phospholipids in the membranes of splenocytes was analyzed by gas chromatography (experiment 1). In addition, the amounts of leukotriene (LT) B(4) and LTB(5) released from peritoneal polymorphonuclear leukocytes (PMNs) were measured by high-performance liquid chromatography (experiment 2).
  
  
  RESULTS
  In experiment 1, after infusion of the fat emulsion containing FO, the omega-3 PUFA content in cell membranes rose to 70% of the peak value on day 1 and nearly reached a plateau on day 3. The highest ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) was achieved by administering a PN solution with the smallest omega-6:omega-3 PUFA ratio. In experiment 2, a larger amount of LTB(5) was released from Ca-ionophore-stimulated PMNs taken from rats given a larger quantity of FO. The ratio of LTB(5):LTB(4) released from PMNs correlated positively with the EPA:AA ratio in the membranous phospholipid and in serum.
  
  
  CONCLUSIONS
  The omega-3 PUFAs were readily incorporated into the cell membrane within 3 days of infusion with the fat emulsion. The EPA:AA ratio in membranous phospholipid in PMNs was positively correlated with the LTB(5):LTB(4) production ratio and was a good indicator of anti-inflammatory effects.
authors.affiliation: R&D Center, Otsuka Pharmaceutical Factory, Inc, Tokushima, Japan. hagiak@otsukakj.co.jp
authors.forename: Akifumi
authors.initials: A
authors.lastname: Hagi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nakayama
authors.forename: Wataru
authors.initials: W
authors.lastname: Shinzaki
authors.forename: Seiji
authors.initials: S
authors.lastname: Haji
authors.forename: Harumasa
authors.initials: H
authors.lastname: Ohyanagi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D005217:Fat Emulsions, Intravenous / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D043371:Fatty Acids, Omega-6 / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D007975:Leukotriene B4 / Q000031:analogs & derivatives / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D010288:Parenteral Nutrition; D010743:Phospholipids / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D005217:Fat Emulsions, Intravenous; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D015289:Leukotrienes; D010743:Phospholipids; D007975:Leukotriene B4; D016718:Arachidonic Acid; C040212:leukotriene B5; D015118:Eicosapentaenoic Acid; D002118:Calcium