Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, The Spanish National Research Council, Seville, Spain.
J Nutr. 2013 May;143(5):620-6. doi: 10.3945/jn.113.174656. Epub 2013 Mar 13.
Postprandial triglyceride (TG)-rich lipoproteins (TRLs) transport dietary fatty acids through the circulatory system to satisfy the energy and structural needs of the tissues. However, fatty acids are also able to modulate gene expression and/or induce cell death. We investigated the underlying mechanism by which postprandial TRLs of different fatty acid compositions can induce cell death in human monocytes. Three types of dietary fat [refined olive oil (ROO), high-palmitic sunflower oil (HPSO), and butter] with progressively increasing SFA:MUFA ratios (0.18, 0.41, and 2.08, respectively) were used as a source of postprandial TRLs (TRL-ROO, TRL-HPSO, and TRL-BUTTER) from healthy men. The monocytic cell line THP-1 was used as a model for this study. We demonstrated that postprandial TRLs increased intracellular lipid accumulation (31-106%), reactive oxygen species production (268-349%), DNA damage (133-1467%), poly(ADP-ribose) polymerase 1 (800-1710%) and caspase-3 (696-1244%) activities, and phosphorylation of c-Jun NH2-terminal kinase (JNK) (54 kDa, 141-288%) and p38 (24-92%). These effects were significantly greater with TRL-BUTTER, and TRL-ROO did not induce DNA damage, DNA fragmentation, or p38 phosphorylation. In addition, blockade of p38, but not of JNK, significantly decreased intracellular lipid accumulation and increased cell death in postprandial TRL-treated cells. These results suggest that in human monocytes, p38 is involved in survival signaling pathways that protect against the lipid-mediated cytotoxicity induced by postprandial TRLs that are abundant in saturated fatty acids.
进食后富含甘油三酯（TG）的脂蛋白（TRLs）通过循环系统将膳食脂肪酸输送到组织中，以满足其能量和结构需求。然而，脂肪酸也能够调节基因表达和/或诱导细胞死亡。我们研究了不同脂肪酸组成的进食后 TRL 如何诱导人单核细胞死亡的潜在机制。三种类型的膳食脂肪[精炼橄榄油（ROO）、高棕榈酸葵花籽油（HPSO）和黄油]具有逐渐增加的 SFA:MUFA 比值（分别为 0.18、0.41 和 2.08），用作健康男性进食后 TRL 的来源（TRL-ROO、TRL-HPSO 和 TRL-BUTTER）。单核细胞系 THP-1 被用作本研究的模型。我们证明，进食后 TRL 增加了细胞内脂质积累（31-106%）、活性氧（ROS）产生（268-349%）、DNA 损伤（133-1467%）、多聚（ADP-核糖）聚合酶 1（PARP1，800-1710%）和半胱天冬酶-3（Caspase-3，696-1244%）活性，以及 c-Jun NH2-末端激酶（JNK，54 kDa）和 p38 的磷酸化（24-92%）。这些作用在 TRL-BUTTER 中更为显著，而 TRL-ROO 不诱导 DNA 损伤、DNA 片段化或 p38 磷酸化。此外，p38 而不是 JNK 的阻断显著减少了细胞内脂质积累并增加了进食后 TRL 处理细胞中的细胞死亡。这些结果表明，在人类单核细胞中，p38 参与了生存信号通路，该通路可防止富含饱和脂肪酸的进食后 TRL 诱导的脂质介导的细胞毒性。
