Possibility of disease prevention by regulating fatty acid nutrition

肿瘤坏死因子（Tumor necrosis factor， TNF）是一种主要的促炎性细胞因子，具有多种功能，其中之一是诱导细胞死亡，包括凋亡和坏死。在这项研究中，我们探讨了二十二碳六烯酸（DHA）和其他多不饱和脂肪酸（PUFAs）对tnf诱导的细胞死亡的影响。用不同的培养细胞检测了DHA预孵育对细胞死亡的影响，并与补充其他脂肪酸的情况进行了比较。细胞与DHA预孵育24小时后，细胞磷脂中DHA含量增加。DHA对tnf诱导的U937细胞凋亡有明显的抑制作用，但对补充二十碳五烯酸（EPA）和花生四烯酸（AA）没有明显的抑制作用。抑制细胞凋亡的同时，DHA在膜磷脂中富集，说明DHA掺入磷脂后发挥了抑制作用。在L929细胞中，TNF可以诱导坏死，这是另一种细胞死亡模式，DHA处理也可以减少这种类型的细胞死亡。与U937细胞凋亡不同，AA显著减弱L929细胞坏死，20:3（n-6）和22:4（n-6）分别表现出相似或更弱的活性。有效PUFA活性的大小顺序为DHA b>二十二碳五烯酸（n-3， DPA）【大于或等于】EPA>AA【约等于】20:3（n-6）【大于或等于】22:4（n-6）。膜磷脂的脂肪酸分析表明，tnf诱导的坏死的衰减主要是由于磷脂中DHA、DPAn-3和AA三种PUFAs的富集。在这些脂肪酸中，DHA在U937凋亡的情况下对L929坏死的减少是最有效的。综上所述，DHA富集膜可以保护细胞免受死亡模式的影响，膜性DHA可以消除坏死和凋亡常见的死亡信号。

Tumor necrosis factor (TNF) is a major pro-inflammatory cytokine with a wide variety of functions, one of which is induction of cell death including apoptosis and necrosis. In this study, we explored effects of docosahexaenoic acid (DHA) and other polyunsaturated fatty acids (PUFAs) on TNF-induced cell death.The effect of preincubation with DHA on cell death was examined using various cultured cells, and compared with the cases of other fatty acids supplementation. Preincubation of cells with DHA for 24 h enriched DHA in cellular phospholipids. DHA showed the distinct ability to reduce TNF-induced apoptosis of U937 cells, but this was not the case in the supplementation of eicosapentaenoic acid (EPA) and arachidonic acid (AA). The inhibition of apoptosis was accompanied by enrichment of DHA in membrane phospholipids, indicating that DHA exerted its inhibitory activity after being incorporated into the phospholipids.In L929 cells, TNF can induce necrosis, another mode of cell death, and DHA treatment could also reduce this type of cell death. Unlike the case of U937 cell apoptosis, AA significantly attenuated L929 cell necrosis, and 20:3(n-6) or 22:4(n-6) showed similar or less activity, respectively. The order of effective PUFA activity was DHA>docosapentaenoic acid (n-3, DPA)【greater than or equal】EPA>AA【approximately equal】20:3(n-6)【greater than or equal】22:4(n-6). Fatty acid analysis of membrane phospholipids suggested that attenuation of TNF-induced necrosis is mainly attributable to the enrichment of three kinds of PUFAs, i.e. DHA, DPAn-3 or AA, in phospholipids. Among these fatty acids, DHA was the most effective in the reduction of L929 necrosis as observed in the case of U937 apoptosis.In summary, DHA-enriched membranes can protect cell irrespective of death modes and membranous DHA may abrogate the death signaling common to necrosis and apoptosis.