ROLE OF ARACHIDONIC-ACID IN THE REGULATION OF THE INFLAMMATORY RESPONSE IN TNF-ALPHA-TREATED RATS

Background: This study examined whether adding arachidonic acid (AA) t o a fish oil diet would alter certain of the anti-inflammatory effects of fish oil in response to tumor necrosis factor(TNF)infusion in rats . Methods: AA was given at 0.08 wt% of let for 6 weeks. The total fat in each diet provided 20% of dietary energy. Four groups were pair-fed sunflower oil (S), S+AA; fish oil (F), or F+AA for 6 weeks. At the en d of feeding, each animal received TNF-alpha (20 mu g/kg) infusion for 3 hours. After 1 hour of TNF infusion, a euglycemic and hyperinsuline mic clamp (10 mU/min per kilogram of insulin) was used to determine th e actions of insulin. The insulin-stimulated glucose utilization in li ver, muscle, and fat was determined by using C-14-deoxyglucose. The pl asma glucose, insulin, and corticosterone levels were determined at ba sal, 60 minutes, and the end of the experiment (180 minutes). The fatt y acid composition of plasma phospholipids also was determined. Result s: Fish oil significantly increased omega-3 fatty acids in phospholipi ds in both F and F+AA and decreased AA in F, compared with S. AA signi ficantly restored the level of AA and reduced the increase of w-3 fatt y acids in phospholipids in F+AA compared with F, but had no impact on fatty acid composition when added to S. Corticosterone level was sign ificantly lower with fish oil feeding but higher in both F and S conta ining AA compared with F and S, respectively. The highest glucose upta ke in tissues was in F, followed by F+AA, and then S and SS AA. Conclu sions: These results suggest that fish oil is anti-inflammatory princi pally through a reduction in the AA content of phospholipids.