Omega-3 Fatty Acids and the Regulation of Expression of Endothelial Pro-Atherogenic and Pro-Inflammatory Genes

G. d'Annunzio University, Chieti, Italy.
Journal of Membrane Biology (Impact Factor: 2.46). 08/2005; 206(2):103-16. DOI: 10.1007/s00232-005-0783-2
Source: PubMed


By partially replacing the corresponding omega-6 analogues in membrane phospholipids, omega-3 fatty acids have been shown to decrease the transcriptional activation of genes--e.g., adhesion molecules, chemoattractants, inflammatory cytokines--involved in endothelial activation in response to inflammatory and pro-atherogenic stimuli. This regulation occurs, at least in part, through a decreased activation of the nuclear factor-kappaB system of transcription factors, secondary to decreased generation of intracellular hydrogen peroxide. Such regulation by omega-3 fatty acids is likely linked to the presence of a higher number of double bonds in the fatty acid chain in omega-3 compared with omega-6 fatty acids. By similar mechanisms, omega-3 fatty acids have been recently shown to reduce gene expression of cyclooxygenase-2, an inflammatory gene involved, through the activation of some metalloproteinases, in plaque angiogenesis and plaque rupture. The quenching of gene expression of pro-inflammatory pro-atherogenic genes by omega-3 fatty acids has consequences on the extent of leukocyte adhesion to vascular endothelium, early atherogenesis and later stages of plaque development and plaque rupture, ultimately yielding a plausible comprehensive explanation for the vasculoprotective effects of these nutrients.

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    • "Clinical benefits of the long-chain omega-3 fatty acids cis-5,8, 11,14,17-eicosapentaenoic acid (EPA) and cis-4,7,10,13,16,19- docosahexaenoic acid (DHA) in the treatment or prevention of disorders such as cardiovascular, Alzheimer's and Parkinson's diseases (Mazza, Pomponi, Janiri, Bria, & Mazza, 2007) have made these fatty acids the subject of intensive research. EPA and DHA have been found to control and regulate various cellular activities, including the expression of an array of important genes in the body (De Caterina & Massaro, 2005). However, humans are unable to de novo synthesise omega-3 fatty acids and poorly convert shortchain omega-3 fatty acids into EPA and DHA. "
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    ABSTRACT: The selectivity of anchovy oil hydrolysis was optimised for Thermomyces lanuginosus lipase, so that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were concentrated and partially separated from each other. Enzyme concentration and pH control were important factors for effective hydrolysis. Monitoring percent hydrolysis using capillary chromatography with flame ionisation detector (Iatroscan) and fatty acid selectivity using gas chromatography (GC) indicated that during hydrolysis DHA primarily remained on the glycerol backbone, while EPA was progressively removed. (13)C nuclear magnetic resonance (NMR) data showed that selectivity of hydrolysis was primarily due to fatty acid selectivity and not regioselectivity, with hydrolysis from both sn-1,3 and sn-2 sites being equally favoured.
    Food Chemistry 05/2013; 138(1):615-20. DOI:10.1016/j.foodchem.2012.11.007 · 3.39 Impact Factor
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    • "FAs are aliphatic monocarboxylic acids that originate from hydrolysis of natural occurring fats and oils (Fahy and others 2009). FAs play various essential biological functions (for example , energy production, membranes structure, cell signaling, immunity , and inflammation) (Woollett and others 1992; Graber and others 1994; Yaqoob 2003; De Caterina and Massaro 2005; Rustan and Drevon 2005). "
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    ABSTRACT: Trans fatty acids (TFAs) mainly arise from 2 major sources: natural ruminal hydrogenation and industrial partial catalytic hydrogenation. Increasing evidence suggests that most TFAs and their isomers cause harmful health effects (that is, increased risk of cardiovascular diseases). Nevertheless, in spite of the existence of an international policy consensus regarding the need for public health action, several countries (for example, France) do not adopt sufficient voluntary approaches (for example, governmental regulations and systematic consumer rejections) nor sufficient industrial strategies (for example, development of healthier manufacturing practices and innovative processes such as fat interesterifications) to eliminate deleterious TFAs from processed foods while ensuring the overall quality of the final product (for example, nutritional value and stability). In this manuscript, we first review the physical-chemical properties of TFAs, their occurrence in processed foods, their main effects on health, and the routine analytical methods to characterize TFAs, before emphasizing on the major industrial methods (that is, fat food reformulation, fat interesterification, genetically modified FAs composition) that can be used worldwide to reduce TFAs in foods.
    Journal of Food Science 03/2013; 78(3):R377-86. DOI:10.1111/1750-3841.12055 · 1.70 Impact Factor
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    • "It is well established that dietary omega-3 fatty acids serve as biological regulators with various physiological roles. They are a fundamental part of the cell membrane, act as signaling molecules, modify gene expression (Price et al. 2000; Deckelbaum et al. 2006; De Caterina and Massaro 2005) and can thereby sustain a status of well-being (Simopoulos 1991; Siddiqui et al. 2004; Connor 2000). Fittingly, omega-3 fatty acids have been established to have a profound correlation with several human diseases. "
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    ABSTRACT: Dietary omega-3 fatty acids have been demonstrated to have positive physiological effects on lipid metabolism, cardiovascular system and insulin resistance. Type-2 diabetes (T2DM) is known for perturbations in fatty acid metabolism leading to dyslipidemia. Our objective was to investigate beneficial effects of dietary flaxseed oil and fish oil in streptozotocin-nicotinamide induced diabetic rats. Thirty-six adult, male, Wistar rats were divided into six groups: three diabetic and three non-diabetic. Diabetes was induced by an injection of nicotinamide (110 mg/kg) and STZ (65 mg/kg). The animals received either control, flaxseed oil or fish oil (10 % w/w) enriched diets for 35 days. Both diets lowered serum triglycerides and very low-density lipoprotein cholesterol levels and elevated serum high-density lipoprotein cholesterol levels in diabetic rats, while serum total cholesterol and LDL-C levels remained unaffected. Both the diets increased omega-3 levels in plasma and RBCs of diabetic rats. Flaxseed oil diet significantly up-regulated the key transcription factor peroxisome proliferator-activated receptor-α (PPAR-α ) and down-regulated sterol regulatory element-binding protein-1 (SREBP-1) in diabetic rats, which would have increased β-oxidation of fatty acids and concomitantly reduced lipogenesis respectively, thereby reducing TG levels. Fish oil diet, on the contrary lowered serum TG levels without altering PPAR-α while it showed a non-significant reduction in SREBP-1 expression in diabetic rats. Another key finding of the study is the activation of D5 and D6 desaturases in diabetic rats by flaxseed oil diet or fish oil diets, which may have resulted in an improved omega-3 status and comparable effects shown by both diets. The reduced expression of Liver-fatty acid binding protein in diabetic rats was restored by fish oil alone, while both diets showed equal effects on adipocyte fatty acid-binding protein expression. We also observed down-regulation of atherogenic cytokines tumor necrosis factor-α and interleukin-6 by both the diets. In conclusion, dietary flaxseed oil and fish oil have therapeutic potential in preventing lipid abnormalities in T2DM.
    Genes & Nutrition 12/2012; 8(3). DOI:10.1007/s12263-012-0326-2 · 2.79 Impact Factor
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