MODIFICATION OF LIVER FATTY-ACID METABOLISM IN MICE BY N-3 AND N-6 DELTA-6-DESATURASE SUBSTRATES AND PRODUCTS

The effects of dietary supplementation of either alpha-linolenic acid (18:3(n - 3)) or stearidonic acid (18:4(n - 3)) in combination with either linoleic acid (18:2(n - 6) or gamma-linolenic acid (18:3(n - 6)) on liver fatty acid composition in mice were examined. Essential fatty acid deficient male C57BL/6 mice were separated into four groups of seven each and were fed a fat-free semi-purified diet supplemented with 1% (w/w) fatty acid methyl ester mixture (1:1), 18:2(n - 6)/18:3(n - 3), 18:2(n - 6)/18:3(n - 6)/18:3(n - 3), or 18:3(n - 6)/18:4(n - 3). After 7 days on the diets, fatty acid compositions in liver phosphatidylcholine and phosphatidylethanolamine fractions were analyzed. In groups fed 18:4(n - 3) (18:2(n - 6)/18:4(n - 3) or 18:3(n - 6)/18:4(n - 3)) as compared to those fed 18:3(n - 3) (18:2(n - 6)/18:3(n -3) or 18:3(n - 6)/18:3(n - 3)), the levels of 20:4(n - 3), 20:5(n - 3) and 22:5(n - 3) were increased, whereas those of 20:3(n - 6) and 20:4(n - 6) were decreased. When 18:3(n - 6) replaced 18:2(n - 6) as the source of n - 6 acids, the levels of 18:3(n - 6), 20:3(n - 6), 20:4(n - 6) and 22:5(n - 6) were increased, whereas those of 20:4(n - 3) and 20:5(n - 3) were reduced. Replacing 18:3(n - 3) by 18:4(n - 3) reduced the (n - 6)/(n - 3) ratio by approx. 30%, whereas replacing 18:2(n - 6) by 18:3(n - 6) increased the (n - 6)/(n - 3) ratio by approx. 2-fold. These findings indicated that DELTA-6-desaturase products were metabolized more readily than their precursors. Both products also competed for the subsequent m metabolic enzymes. However, the n - 6 fatty acids derived from 18:3(n - 6) were incorporated more favourably into liver phospholipids than n - 3 fatty acids derived from 18:4(n - 3).