DIETARY FISH-OIL INHIBITS DELTA-6-DESATURASE ACTIVITY IN-VIVO

Liver Delta d6-desaturase activity was determined in mice which were m ade 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) die t during the refeeding period. This 1-wk fasting/refeeding protocol, r eferred 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 acid s, notably oleic acid and Mead acid (20:3n-9). Combined liver Delta 6d esaturase/elongase/Delta 5-desaturase activities in vivo were quantifi ed by measuring the conversion of C-14-linoleic acid (LA) to C-14-AA i n mouse liver. Although F/R EFAD caused, as expected, a substantial de cline in liver AA and LA content, the conversion of C-14-LA to C-14-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, supple mented with corn oil, restored tissue n-6 PUFA levels without altering the conversion of C-14-LA to C-14-AA. In contrast, refeeding with an EFAD diet, supplemented with fish oil, inhibited C-14-LA to C-14-AA co nversion by 78%. Significantly, inhibition of conversion of C-14-LA to C-14-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 PU FA were increa sed. The data suggest that dietary n-3 C20-22 PUFA negatively regulate the in vivo synthesis of n-6 PUFA at the level of the Delta 6-desatur ase.