Endogenous production of n-3 and n-6 fatty acids in mammalian cells

Polyunsaturated fatty acids (PUFA) are important components of mammalian diets, and the beneficial effects of n-3 PUFA on human development and cardiovascular health have been well documented. Caenorhabditis elegans is one of the few animals known to be able to produce linoleic (LA, 18:2n-6) and alpha-linolenic (ALA, 18:3n-3) essential fatty acids. These essential PUFA are generated by the action of desaturases that successively direct the conversion of monounsaturated fatty acids (MUFA) to PUFA. The cDNA coding sequences of the C. elegans Delta(12) and n-3 fatty acid desaturases were each placed under the control of separate constitutive eukaryotic promoters and simultaneously introduced into HC11 mouse mammary epithelial cells by adenoviral transduction. Phospholipids from transduced cells showed a significant decrease in the ratios of both MUFA:PUFA and n-6:n-3 fatty acids relative to control cultures. The fatty acid profile of transduced cellular phospholipids revealed significant decreases in MUFA and arachidonic acid (20:4n-6), and increases in LA, ALA, and eicosapentaenoic acid (20:5n-3). The fatty acid composition of triacylglycerols derived from transduced cells was similarly, but less dramatically, affected. These results demonstrate the functionality of C. elegans fatty acid desaturase enzymes in mammalian cells. Expression of these desaturases in livestock might act to counterbalance the saturating effect that rumen microbial biohydrogenation has on the fatty acid profile of ruminant products, and allow for the development of novel, land-based dietary sources of n-3 PUFA.