Exogenous tetracosahexaenoic acid modifies the fatty acid composition of human primary T lymphocytes and Jurkat T cell leukemia cells contingent on cell type

Abstract

Tetracosahexaenoic acid (24:6ω-3) is an intermediate in the conversion of 18:3ω-3 to 22:6ω-3 in mammals. There is limited information about whether cells can assimilate and metabolize exogenous 24:6ω-3. This study compared the effect of incubation with 24:6ω-3 on the fatty acid composition of two related cell types, primary CD3⁺ T lymphocytes and Jurkat T cell leukemia, which differ in the integrity of the polyunsaturated fatty acid (PUFA) biosynthesis pathway. 24:6ω-3 was only detected in either cell type when cells were incubated with 24:6ω-3. Incubation with 24:6ω-3 induced similar increments in the amount of 22:6ω-3 in both cell types and modified the homeoviscous adaptations fatty acid composition induced by activation of T lymphocytes. The effect of incubation with 18:3ω-3 compared to 24:6ω-3 on the increment in 22:6ω-3 was tested in Jurkat cells because primary T cells cannot convert 18:3ω-3 to 22:6ω-3. The increment in the 22:6ω-3 content of Jurkat cells incubated with 24:6ω-3 was 19.5-fold greater than that of cells incubated with 18:3ω-3. Acyl-coA oxidase siRNA knockdown decreased the amount of 22:6ω-3 and increased the amount of 24:6ω-3 in Jurkat cells. These findings show exogenous 24:6ω-3 can be incorporated into primary human T lymphocytes and Jurkat cells and induces changes in fatty acid composition consistent with its conversion to 22:6ω-3 via a mechanism involving peroxisomal β-oxidation that is regulated independently from the integrity of the upstream PUFA synthesis pathway. One further implication is that consuming 24:6ω-3 may be an effective alternative means of achieving health benefits attributed to 20:5ω-3 and 22:6ω-3.