METABOLISM OF LINOLEIC AND ALPHA-LINOLENIC ACIDS IN CULTURED CARDIOMYOCYTES - EFFECT OF DIFFERENT N-6 AND N-3 FATTY-ACID SUPPLEMENTATION

The metabolites of linoleic (LA) and alpha-linolenic (ALA) acids are i nvolved in coronary heart disease. Both n-6 and n-3 essential fatty ac ids (EFAs) are likely to be important in prevention of atherosclerosis since the common risk factors are associated with their reduced 6-des aturation. We previously demonstrated the ability of heart tissue to d esaturate LA. In this study we examined the ability of cultured cardio myocytes to metabolize both LA and ALA in vivo, in the absence and in the presence of gamma linolenic acid (GLA), eicosapentaenoic acid (EPA ), docosahexaenoic acid (DHA) alone or combined together. In control c onditions, about 25% of LA and about 90% of ALA were converted in PUFA s. GLA supplementation had no influence on LA conversion to more unsat urated fatty acids, while the addition of n-3 fatty acids, alone or co mbined together, significantly decreased the formation of interconvers ion products from LA. Using the combination of n-6 and n-3 PUFAs, GLA seemed to counterbalance partially the inhibitory effect of EPA and DH A on LA desaturation/elongation. The conversion of ALA to more unsatur ated metabolites was greatly affected by GLA supplementation. Each sup plemented fatty acid was incorporated to a significant extent into car diomyocyte lipids, as revealed by gas chromatographic analysis. The n- 6/n-3 fatty acid ratio was greatly influenced by the different supplem entations; the ratio in GLA+EPA+DHA supplemented cardiomyocytes was th e most similar to that recorded in control cardiomyocytes. Since impor tant risk factors for coronary disease may be associated with reduced 6-desaturation of the parent EFAs, administration of n-6 or n-3 EFA me tabolites alone could cause undesirable effects. Since they appear to have different and synergistic roles, only combined treatment with bot h n-6 and n-3 metabolites is likely to achieve optimum results.