School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK.
Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
Lipids. 2023 Jul;58(4):185-196. doi: 10.1002/lipd.12372. Epub 2023 May 13.
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.
二十四碳六烯酸(24:6ω-3)是哺乳动物将 18:3ω-3 转化为 22:6ω-3 的中间产物。目前关于细胞是否能够吸收和代谢外源性 24:6ω-3 的信息有限。本研究比较了孵育 24:6ω-3 对两种相关细胞类型——原代 CD3 T 淋巴细胞和 Jurkat T 细胞白血病——脂肪酸组成的影响,这两种细胞类型在多不饱和脂肪酸(PUFA)生物合成途径的完整性上存在差异。只有当细胞孵育 24:6ω-3 时,24:6ω-3 才会在这两种细胞类型中被检测到。孵育 24:6ω-3 可使两种细胞类型中 22:6ω-3 的含量相似增加,并改变 T 淋巴细胞激活诱导的同型粘弹性适应脂肪酸组成。在 Jurkat 细胞中测试了与 18:3ω-3 孵育相比 24:6ω-3 对 22:6ω-3 增加的影响,因为原代 T 细胞不能将 18:3ω-3 转化为 22:6ω-3。与孵育 18:3ω-3 的 Jurkat 细胞相比,孵育 24:6ω-3 可使 Jurkat 细胞中 22:6ω-3 的含量增加 19.5 倍。酰基辅酶 A 氧化酶 siRNA 敲低降低了 Jurkat 细胞中 22:6ω-3 的含量,并增加了 24:6ω-3 的含量。这些发现表明,外源性 24:6ω-3 可以被整合到原代人 T 淋巴细胞和 Jurkat 细胞中,并诱导脂肪酸组成的变化,这与通过涉及过氧化物酶体β-氧化的机制将其转化为 22:6ω-3 一致,该机制独立于上游 PUFA 合成途径的完整性。另一个含义是,摄入 24:6ω-3 可能是一种有效替代途径,可获得归因于 20:5ω-3 和 22:6ω-3 的健康益处。