Adenoviral gene transfer of Caenorhabditis elegans n-3 fatty acid desaturase optimizes fatty acid composition in mammalian cells

Omega-3 polyunsaturated fatty acids (PUFAs) are essential components requir ed for normal cellular function and have been shown to exert many preventiv e and therapeutic actions. The amount of n-3 PUFAs is insufficient in most Western people, whereas the level of n-6 PUFAs is relatively too high, with an n-6/n-3 ratio of >18. These two classes of PUFAs are metabolically and functionally distinct and often have important opposing physiological funct ions; their balance is important for homeostasis and normal development. El evating tissue concentrations of n-3 PUFAs in mammals relies on chronic die tary intake of fat rich in n-3 PUFAs, because mammalian cells lack enzymati c activities necessary either to synthesize the precursor of n-3 PUFAs or t o convert n-6 to n-3 PUFAs. Here we report that adenovirus-mediated introdu ction of the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid d esaturase into mammalian cells can quickly and effectively elevate the cell ular n - 3 PUFA contents and dramatically balance the ratio of n-6/n-3 PUFA s, Heterologous expression of the fat-1 gene in rat cardiac myocytes render ed cells capable of converting various n-6 PUFAs to the corresponding n-3 P UFAs, and changed the n-6/n-3 ratio from about 15:1 to 1:1. In addition, an eicosanoid derived from n-6 PUFA (i.e., arachidonic acid) was reduced sign ificantly in the transgenic cells. This study demonstrates an effective app roach to modifying fatty acid composition of mammalian cells and also provi des a basis for potential applications of this gene transfer in experimenta l and clinical settings.