Effects of n-3 polyunsaturated fatty acids on cellular phenotypes and molecular mechanisms.

脂肪酸（FA）是传统上被认为代表参与几种生物体能量产生和储存的中间代谢产物的食物组分。它们也是细胞膜的重要组成部分。现在已经非常清楚，它们可以通过多种机制影响细胞功能。包括我们在内的几个研究小组报告说，使用鱼油胶囊补充omega-3多不饱和脂肪酸（n-3 PUFA）对心血管健康有有益的影响，并大大改变了各种人体组织中的基因表达。由于n-3 PUFA是通过饮食或作为胶囊中的纯化提取物获得的，因此难以研究每种n-3 PUFA的独立作用并阐明其组织和细胞特异性作用。我们的研究计划旨在通过开发一个平台来评估受脂肪酸影响的细胞表型和分子机制，特别是来自植物（α亚麻酸（ALA））和海洋（二十碳五烯酸（EPA）和二十二碳六烯酸（DHA））来源的n-3 PUFA。** 本发现计划的具体目标是：*1）-表征与免疫细胞中三种不同n-3 PUFA（ALA、EPA和DHA）的独立作用相关的细胞表型。广泛的细胞表型将用于确定和比较不同n-3 PUFA的作用。*2）-使用基因表达和功能分析将细胞表型与免疫细胞中特定细胞机制的激活相关联。基因表达分析将用于确定不同n-3 PUFA对细胞机制的特定影响，并突出n-3 PUFA依赖性细胞机制。功能分析将用于将细胞表型与基因表达谱联系起来。** 这项研究计划将导致更好地了解n-3 PUFA对细胞表型和分子机制的影响。这将有助于阐明潜在的机制，解释细胞和分子的变化归因于每个n-3 PUFA。本研究为其他生物活性脂质在细胞和分子水平上的生物学效应研究奠定了基础。在全球范围内，它将通过开发一个易于适应各种食物成分和不同细胞模型的分析平台，加快专注于单个食物成分影响的研究领域。这可能会通过影响食品开发行业和预防/治疗方法的发展而影响到人口。**

Fatty acids (FA) are food components traditionally thought to represent intermediary metabolites involved in energy production and storage in several living organisms. They are also important components of cell membranes. It has now become very clear that they can influence cell function through a variety of mechanisms. Several research groups including ours have reported that omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation using fish oil capsules have beneficial effects on cardiovascular health and substantially alter gene expression in various human tissues. As n-3 PUFAs are obtained through diet or as purified extracts in capsules for supplementation, it is difficult to study the independent effect of each n-3 PUFAs and to elucidate their tissue- and cell-specific effects. Our research program aims to build knowledge on the mechanism of action of lipid mediators through the development of a platform to assess cellular phenotypes and molecular mechanisms influenced by FAs, and particularly of n-3 PUFAs from vegetal (alpha linolenic acid (ALA)) and marine (eicosapentanoic acid (EPA) and docosahexanoic acid (DHA)) sources. ******The specific objectives of this discovery program are: ***1)- To characterize cellular phenotypes associated with the independent effects of three different n-3 PUFAs (ALA, EPA and DHA) in immune cells. Extensive cellular phenotyping will be used to determine and compare effects of different n-3 PUFAs. ***2)- To relate cellular phenotypes to the activation of specific cellular mechanisms in immune cells using gene expression and functional analyses. Gene expression analyses will be used to identify specific effects of the different n-3 PUFAs on cellular mechanisms and to highlight n-3 PUFA-dependent cellular mechanisms. Functional analyses will be used to link cellular phenotypes to gene expression profiles. ******This research program will lead to a better knowledge of the effects of n-3 PUFAs on cellular phenotypes and molecular mechanisms. It will contribute to elucidate the underlying mechanisms explaining cellular and molecular changes attributable to each n-3 PUFAs. Our study will pave the way for studies on the biological effects at the cellular and molecular levels of other bioactive lipids. Globally, it will speed up research field focusing on the effects of individual food components through the development of an analysis platform easily adaptable to various food components and different cellular models. This is likely to impact at population levels through an influence on food development industry and the development of prevention/therapeutic approaches. **