Possibility of disease prevention by regulating fatty acid nutrition

肿瘤坏死因子是一种主要的促炎细胞因子，具有多种功能，其中之一是诱导细胞死亡，包括细胞凋亡和坏死。本研究探讨了二十二碳六烯酸(DHA)和其他多不饱和脂肪酸(PUFAs)对肿瘤坏死因子诱导的细胞死亡的影响。通过不同培养细胞的实验，观察了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。将细胞与DHA预孵育24小时，使细胞磷脂中的DHA含量增加。DHA对肿瘤坏死因子诱导的U937细胞凋亡有明显的抑制作用，但二十碳五烯酸(EPA)和花生四烯酸(AA)的作用不明显。细胞凋亡的抑制伴随着DHA在膜磷脂中的聚集，说明DHA进入磷脂后发挥了抑制作用。在L929细胞中，肿瘤坏死因子可以诱导另一种细胞死亡方式，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能显著减轻L929细胞的坏死，20：3(n-6)和22：4(n-6)的活性相近或更弱。有效的多不饱和脂肪酸活性顺序为DHA和GT；二十二碳五烯酸(n-3，DPA)[大于或等于]EPA和GT；AA[大致相等]20：3(n-6)[大于或等于]22：4(n-6)。膜磷脂的脂肪酸分析表明，减轻肿瘤坏死主要是由于磷脂中富含DHA、DPAn-3或AA三种多不饱和脂肪酸所致。在这些脂肪酸中，DHA是最有效的减少L929细胞坏死的作用，在U937细胞凋亡的情况下观察到。综上所述，DHA富集膜可以保护细胞不受死亡模式的影响，膜DHA可能取消坏死和凋亡共同的死亡信号。

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.