Rundblad Amanda, Larsen Sunniva V, Myhrstad Mari C, Ottestad Inger, Thoresen Magne, Holven Kirsten B, Ulven Stine M
1Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, PO Box 1046, Blindern, 0317 Oslo, Norway.
2Department of Nursing and Health Promotion, Faculty of Health Sciences, OsloMet - Oslo Metropolitan University, PO Box 4, St Olavs plass, 0130 Oslo, Norway.
Genes Nutr. 2019 Apr 25;14:10. doi: 10.1186/s12263-019-0633-y. eCollection 2019.
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.
In a previous randomized controlled trial, healthy normotriglyceridemic subjects ( = 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.
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 ( ≤ 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 ( ≤ 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.
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.
Based on free images from Servier Medical Art (Creative Commons Attribution License) and image from www.colourbox.com.
摄入海洋ω-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，从而可能降低心血管疾病风险。然而，ω-3补充剂的TG降低效果存在较大个体差异。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-环境相互作用可能也很重要。在本研究中，我们旨在调查ω-3脂肪酸补充剂的TG反应者和非反应者之间外周血单个核细胞（PBMC）基因表达和脂蛋白亚类TG水平的基线差异及变化差异。
在之前的一项随机对照试验中，健康的正常甘油三酯血症受试者（n = 35，71%为女性）每天服用1.6 g EPA + DHA，持续7周。在这项探索性子研究中，我们将TG反应者定义为TG降低超过每日20%变化的受试者，将非反应者定义为ω-3补充后TG变化在-20%至+20%之间的受试者。使用微阵列测量PBMC基因表达，使用核磁共振波谱法测量脂蛋白亚类。
8名受试者被定义为反应者，TG中位数降低37%，16名受试者被定义为非反应者，TG中位数变化为0%。在基线时，反应者在四个高密度脂蛋白（HDL）亚类中的两个中TG水平较高，与非反应者相比，有909个基因转录本（P≤0.05）差异表达。在干预期间，反应者血浆TG的降低反映在六个不同的极低密度脂蛋白亚类中的四个以及四个不同的HDL亚类中的三个的TG降低。与非反应者相比，反应者中有454个转录本的表达有差异改变（P≤0.05）。通路分析显示，反应者的信号通路与发育和免疫功能相关。此外，与非反应者相比，反应者中富集程度最高的前10条通路中有两条与溶血磷脂酸信号传导有关。
ω-3补充剂的TG反应者和非反应者在基线时具有不同的脂蛋白亚类和PBMC基因表达谱，对ω-3补充剂的脂蛋白亚类和PBMC基因表达反应也不同。这些基因表达差异可能部分解释了ω-3补充后观察到的TG反应变异性。
基于Servier Medical Art的免费图像（知识共享署名许可）和来自www.colourbox.com的图像。
