Dietary fish oil inhibits Δ6‐desaturase activity in vivo

Abstract

AbstractLiver 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‐LA to 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 C20–22 PUFA negatively regulate the in vivo synthesis of n‐6 PUFA at the level of the Δ6‐desaturase.