Background Intake of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduces fasting triglyceride (TG) levels and may thereby lower cardiovascular disease risk. However, there are large inter-individual differences in the TG-lowering effect of omega-3 supplementation. Genotype differences partly explain this variation, but gene-environment interactions leading to gene expression differences may also be important. In this study, we aimed to investigate baseline differences and differences in the change in peripheral blood mononuclear cell (PBMC) gene expression and lipoprotein subclass TG levels between TG responders and non-responders to omega-3 fatty acid supplementation. Methods In a previous randomized controlled trial, healthy normotriglyceridemic subjects (n = 35, 71% women) received 1.6 g EPA + DHA/day for 7 weeks. In this exploratory sub-study, we defined TG responders as subjects having a TG reduction beyond the 20% day-to-day variation and non-responders as having a TG change between - 20% and + 20% after omega-3 supplementation. PBMC gene expression was measured using microarray, and lipoprotein subclasses were measured using nuclear magnetic resonance spectroscopy. Results Eight subjects were defined as responders with a median TG reduction of 37%, and 16 subjects were defined as non-responders with a median TG change of 0%. At baseline, responders had higher TG levels in two of four high-density lipoprotein (HDL) subclasses and 909 gene transcripts (p ≤ 0.05) were differentially expressed compared to non-responders. During the intervention, the plasma TG reduction among responders was reflected in TG reductions in four of six different very low-density lipoprotein subclasses and three of four different HDL subclasses. Compared to non-responders, the expression of 454 transcripts was differentially altered in responders (p ≤ 0.05). Pathway analyses revealed that responders had altered signaling pathways related to development and immune function. In addition, two of the top 10 enriched pathways in responders compared to non-responders were related to lysophosphatidic acid signaling. Conclusion TG responders and non-responders to omega-3 supplementation have different lipoprotein subclass and PBMC gene expression profiles at baseline and different lipoprotein subclass and PBMC gene expression responses to omega-3 supplementation. These gene expression differences may partially explain the variability in TG response observed after omega-3 supplementation. Graphical abstract Based on free images from Servier Medical Art (Creative Commons Attribution License) and image from www.colourbox.com.

中文翻译：

---

对 omega-3 补充剂有反应的血浆甘油三酯反应者和无反应者的外周血单核细胞基因表达和脂蛋白亚类中甘油三酯组成的差异。

背景 摄入海洋 omega-3 脂肪酸二十碳五烯酸 (EPA) 和二十二碳六烯酸 (DHA) 可降低空腹甘油三酯 (TG) 水平，从而降低心血管疾病风险。然而，omega-3 补充剂的 TG 降低效果存在很大的个体差异。基因型差异部分解释了这种变异，但导致基因表达差异的基因 - 环境相互作用也可能很重要。在本研究中，我们旨在调查 TG 应答者和 omega-3 脂肪酸补充剂无应答者之间外周血单个核细胞 (PBMC) 基因表达和脂蛋白亚类 TG 水平变化的基线差异和差异。方法 在之前的一项随机对照试验中，健康的甘油三酯正常受试者（n = 35，71% 的女性）接受了 1。6 克 EPA + DHA/天，持续 7 周。在这项探索性子研究中，我们将 TG 响应者定义为 TG 降低超过 20% 的日常变化的受试者，而无响应者定义为在补充 omega-3 后 TG 变化在 - 20% 和 + 20% 之间的受试者。PBMC 基因表达使用微阵列测量，脂蛋白亚类使用核磁共振波谱测量。结果 8 名受试者被定义为中位 TG 降低 37% 的反应者，16 名受试者被定义为中位 TG 变化为 0% 的无反应者。在基线时，与无应答者相比，应答者在四个高密度脂蛋白 (HDL) 亚类中的两个中具有较高的 TG 水平，并且 909 个基因转录本 (p ≤ 0.05) 表达差异。干预期间，应答者的血浆 TG 降低反映在 6 种不同的极低密度脂蛋白亚类中的 4 种和 4 种不同 HDL 亚类中的 3 种 TG 降低。与无应答者相比，应答者中 454 个转录本的表达发生了不同的变化（p ≤ 0.05）。通路分析显示，应答者改变了与发育和免疫功能相关的信号通路。此外，与无应答者相比，应答者的前 10 种富集途径中有两条与溶血磷脂酸信号传导有关。结论 对 omega-3 补充剂的 TG 反应者和无反应者在基线时具有不同的脂蛋白亚类和 PBMC 基因表达谱，并且对 omega-3 补充剂有不同的脂蛋白亚类和 PBMC 基因表达反应。这些基因表达差异可以部分解释补充 omega-3 后观察到的 TG 反应的变异性。图形摘要基于来自 Servier Medical Art（知识共享署名许可）的免费图片和来自 www.colourbox.com 的图片。