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Effects of the ω‐6:ω‐3 Fatty Acid Ratio of Fat Emulsions on the Fatty Acid Composition in Cell Membranes and the Anti‐Inflammatory Action
Authors:Akifumi Hagi PhD  Mitsuo Nakayama PhD  Wataru Shinzaki MD  Seiji Haji MD  PhD  Harumasa Ohyanagi MD  PhD
Institution:1. R&D Center, Otsuka Pharmaceutical Factory, Inc, Tokushima, Japan;2. Department of Surgery, Kinki University School of Medicine, Osaka, Japan
Abstract:Background: This study investigated the effects of parenterally administered fish oil (FO) on the fatty acid composition in rats to determine the optimal ω‐6:ω‐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 ω‐6:ω‐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) B4 and LTB5 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 ω‐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 administrating a PN solution with the smallest ω‐6:ω‐3 PUFA ratio. In experiment 2, a larger amount of LTB5 was released from Ca‐ionophore‐stimulated PMNs taken from rats given a larger quantity of FO. The ratio of LTB5:LTB4 released from PMNs correlated positively with the EPA:AA ratio in the membranous phospholipid and in serum. Conclusions: The ω‐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 LTB5:LTB4 production ratio and was a good indicator of anti‐inflammatory effects.
Keywords:fat emulsion  fish oil  ω  ‐6:ω  ‐3 PUFA ratio  EPA  AA  eicosanoids production
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