α-亚麻酸和二十二碳六烯酸对THP-1单核细胞及肥胖人群免疫细胞中胆固醇代谢相关基因表达及感染反应的不同影响。
Distinct effects of α-linolenic acid and docosahexaenoic acid on the expression of genes related to cholesterol metabolism and the response to infection in THP-1 monocytes and immune cells of obese humans.
作者信息
Rodway Lisa A, Pauls Samantha D, Pascoe Christopher D, Aukema Harold M, Taylor Carla G, Zahradka Peter
机构信息
Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada.
Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada; Department of Food and Human Nutritional Sciences, Faculty of Agricultural and Food Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
出版信息
Biomed Pharmacother. 2023 Mar;159:114167. doi: 10.1016/j.biopha.2022.114167. Epub 2023 Jan 6.
BACKGROUND
Monocytes play a large role in chronic inflammatory conditions such as obesity, atherosclerosis and infection. Marine-derived omega-3 fatty acids such as docosahexaenoic acid (DHA) beneficially alter immune function and attenuate chronic inflammation in part by modifying gene expression. Comparisons with plant-derived omega-3 α-linolenic acid (ALA) on immune cell gene expression and function are limited.
METHODS
Transcriptome analysis was performed on THP-1 human monocytes treated with ALA, DHA or vehicle for 48 hr using fold change analysis, principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), variable importance analysis (VIP), and ingenuity pathway analysis (IPA). Candidate genes were validated by qPCR. Functional assays evaluated the transcriptomic predictions. Expression of candidate transcripts identified in THP-1 cells were examined in PBMC from clinical trial (OXBIO; NCT03583281) participants consuming ALA- or DHA-rich oil supplements.
FINDINGS
ALA and DHA-treated monocytes presented distinct transcriptomic profiles as per VIP and PLS-DA. Both fatty acids were predicted to reduce cellular cholesterol content, while ALA would uniquely increase response to infection and chemotactic signals. Functional assays revealed ALA and DHA decreased cholesterol content. DHA significantly decreased the response to infection and chemotaxis, but ALA had no effect. Candidate transcripts responded similarly in PBMC from n-3 PUFA supplemented women with obesity.
CONCLUSION
ALA and DHA differentially alter the transcription profiles and functions associated with the response to infection, chemotaxis, and cholesterol metabolism in mononuclear immune cells. Thus, they may uniquely affect related disease processes contributing to obesity, atherosclerosis, and the response to infection.
背景
单核细胞在肥胖、动脉粥样硬化和感染等慢性炎症性疾病中起重要作用。海洋来源的ω-3脂肪酸，如二十二碳六烯酸（DHA），可有益地改变免疫功能，并部分通过修饰基因表达来减轻慢性炎症。关于植物来源的ω-3α-亚麻酸（ALA）对免疫细胞基因表达和功能影响的比较研究有限。
方法
使用倍数变化分析、主成分分析（PCA）、偏最小二乘判别分析（PLS-DA）、变量重要性分析（VIP）和 Ingenuity 通路分析（IPA），对用 ALA、DHA 或载体处理 48 小时的 THP-1 人单核细胞进行转录组分析。通过 qPCR 验证候选基因。功能测定评估转录组预测结果。在食用富含 ALA 或 DHA 油补充剂的临床试验（OXBIO；NCT03583281）参与者的外周血单核细胞（PBMC）中检测 THP-1 细胞中鉴定出的候选转录本的表达。
研究结果
根据 VIP 和 PLS-DA，ALA 和 DHA 处理的单核细胞呈现出不同的转录组图谱。两种脂肪酸都被预测会降低细胞胆固醇含量，而 ALA 会独特地增加对感染和趋化信号的反应。功能测定显示 ALA 和 DHA 降低了胆固醇含量。DHA 显著降低了对感染和趋化性的反应，但 ALA 没有影响。在补充 n-3 多不饱和脂肪酸的肥胖女性的 PBMC 中，候选转录本的反应相似。
结论
ALA 和 DHA 以不同方式改变与单核免疫细胞对感染、趋化性和胆固醇代谢反应相关的转录谱和功能。因此，它们可能独特地影响与肥胖、动脉粥样硬化和感染反应相关的疾病进程。
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