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) to 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 diet 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 end of feeding, each animal received TNF-alpha (20 microg/kg) infusion for 3 hours. After 1 hour of TNF infusion, a euglycemic and hyperinsulinemic clamp (10 mU/min per kilogram of insulin) was used to determine the actions of insulin. The insulin-stimulated glucose utilization in liver, muscle, and fat was determined by using 14C-deoxyglucose. The plasma glucose, insulin, and corticosterone levels were determined at basal, 60 minutes, and the end of the experiment (180 minutes). The fatty acid composition of plasma phospholipids also was determined.


RESULTS
Fish oil significantly increased omega-3 fatty acids in phospholipids in both F and F+AA and decreased AA in F, compared with S. AA significantly restored the level of AA and reduced the increase of omega-3 fatty acids in phospholipids in F+AA compared with F, but had no impact on fatty acid composition when added to S. Corticosterone level was significantly lower with fish oil feeding but higher in both F and S containing AA compared with F and S, respectively. The highest glucose uptake in tissues was in F, followed by F+AA, and then S and S+AA.


CONCLUSIONS
These results suggest that fish oil is anti-inflammatory principally through a reduction in the AA content of phospholipids.
Ling
P R
PR
Nutrition/Infection Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Boyce
P
P
Bistrian
B R
BR
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000097:blood; D005395:Fish Oils / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism; D010743:Phospholipids / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha
D001786:Blood Glucose; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D007328:Insulin; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha; D016718:Arachidonic Acid; D005947:Glucose