Arachidonic acid and docosahexaenoic acid supplemented to an essential fatty acid-deficient diet alters the response to endotoxin in rats

This study examined fatty acid profiles, triene-tetraene ratios (20:3n9/20:4n6), and nutritional and inflammatory markers in rats fed an essential fatty acid-deficient (EFAD) diet provided as 2% hydrogenated coconut oil (HCO) alone for 2 weeks or with 1.3 mg of arachidonic acid (AA) and 3.3 mg of docosahexaenoic acid (DHA) (AA + DHA) added to achieve 2% fat. Healthy controls were fed an AIN 93M diet (AIN) with 2% soybean oil. The HCO and AA + DHA diets led to significant reductions of linoleic acid, α-linolenic acid, and AA (20:4n6) and increases in Mead acid (20:3n9) in plasma and liver compared with the AIN diet; but the triene-tetraene levels remained well within normal. However, levels of 20:3n9 and 20:4n6 were lower in liver phospholipids in the AA + DHA than in HCO group, suggesting reduced elongation and desaturation in ω-9 and -6 pathways. The AA + DHA group also had significantly lower levels of 18:1n9 and 16:1n7 as well as 18:1n9/18:0 and 16:1n7/16:0 than the HCO group, suggesting inhibition of stearyl-Co A desaturase-1 activity. In response to lipopolysaccharide, the levels of tumor necrosis factor and interleukin-6 were significantly lower with HCO, reflecting reduced inflammation. The AA + DHA group had higher levels of IL-6 and C-reactive protein than the HCO group but significantly lower than the AIN group. However, in response to endotoxin, interleukin-6 was higher with AA + DHA than with AIN. Feeding an EFAD diet reduces baseline inflammation and inflammatory response to endotoxin long before the development of EFAD, and added AA + DHA modifies this response.