Dietary fish oil inhibits Δ6-desaturase activity in vivo

Liver Δ6-desaturase activity was determined in mice which were made deficient in (i) n-6 and n-3 polyunsaturated fatty acids (PUFA), (ii) n-6 PUFA, or (iii) arachidonic acid (AA). Initially, the mice were subjected to two cycles of a fasting (1 d)/refeeding (2-3 d) protocol in which they were refed an essential fatty acid-deficient (EFAD) diet during the refeeding period. This 1-wk fasting/refeeding protocol, referred to as F/R EFAD, produced a rapid and substantial decline in tissue n-3 and n-6 PUFA and a corresponding increase in n-9 fatty acids, notably oleic acid and Mead acid (20:3n-9). Combined liver Δ6-desaturase/elongase/Δ5-desaturase activities in vivo were quantified by measuring the conversion of ¹⁴C-linoleic acid (LA) to ¹⁴C-AA in mouse liver. Although F/R EFAD caused, as expected, a substantial decline in liver AA and LA content, the conversion of ¹⁴C-LA to ¹⁴C-AA was the same in these mice as in chow-fed controls (approximately 33-34%). Subsequent refeeding of F/R EFAD mice with an EFAD diet, supplemented with corn oil, restored tissue n-6 PUFA levels without altering the conversion of ¹⁴C-LAto ¹⁴C-AA. In contrast, refeeding with an EFAD diet, supplemented with fish oil, inhibited ¹⁴C-LA to ¹⁴C-AA conversion by 78%. Significantly, inhibition of conversion of ¹⁴C-LA to ¹⁴C-AA was maintained in F/R EFAD mice that were subsequently fed an EFAD diet supplemented with a 1:1 mixture of fish oil/corn oil. This latter protocol yielded a unique liver fatty acid composition in which AA was selectively depleted, whereas LA and the n-3 PUFA were increased. The data suggest that dietary n-3 C_20-22 PUFA negatively regulate the in vivo synthesis of n-6 PUFA at the level of the Δ6-desaturase. Desaturase, essential fatty acid-deficient, fish oil, n-6/n-3 polyunsaturated fatty acids.