docosapentaenoic-acid and Inflammation

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 polyunsaturated fatty acids (PUFAs) consumed in low abundance in the Western diet. Increased consumption of n-3 PUFAs may have beneficial effects for a wide range of physiological outcomes including chronic inflammation. However, considerable mechanistic gaps in knowledge exist about EPA versus DHA, which are often studied as a mixture. We suggest the novel hypothesis that EPA and DHA may compete against each other through overlapping mechanisms. First, EPA and DHA may compete for residency in membrane phospholipids and thereby differentially displace n-6 PUFAs, which are highly prevalent in the Western diet. This would influence biosynthesis of downstream metabolites of inflammation initiation and resolution. Second, EPA and DHA exert different effects on plasma membrane biophysical structure, creating an additional layer of competition between the fatty acids in controlling signaling. Third, DHA regulates membrane EPA levels by lowering its rate of conversion to EPA's elongation product n-3 docosapentaenoic acid. Collectively, we propose the critical need to investigate molecular competition between EPA and DHA in health and disease, which would ultimately impact dietary recommendations and precision nutrition trials.

Topics: Animals; Arachidonic Acid; Diet; Diet, Western; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Humans; Inflammation; Phospholipids

The review presents recent developments in the identification of specialized proresolving mediators (SPMs) of inflammation following supplementation with n-3 fatty acids in humans.. A number of reports have measured SPMs in human plasma after n-3 fatty acid supplementation. Although studies have shown some variability in plasma SPM levels, there is strong evidence that a number of resolvins are increased after n-3 fatty acids to concentrations that have been shown to have biological activity. SPM concentrations at the inflammatory site would be expected to be higher than that in blood. SPMs derived from docosapentaenoic acid require further investigation.. Resolution of inflammation is an active process with SPM playing a vital role in maintaining homeostasis. Studies in humans are providing evidence to suggest that this may be a relevant mechanism that can be stimulated by n-3 fatty acid supplementation. Further research is now required to determine SPM profiles in patients with different chronic conditions and to examine whether supplementation with n-3 fatty acids affects SPMs in relation to their clinical outcome.

Topics: Animals; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Humans; Inflammation; Inflammation Mediators

Docosapentaenoic acid (DPA) is a long-chain n-3 polyunsaturated fatty acid that is intermediary between eicosapentaenoic acid and docosahexaenoic acid in the n-3 synthesis pathway. DPA is part of our normal diet through fish and lean red meat. In recent years, DPA has received increasing attention as an important bioactive fatty acid in light of its potential beneficial health effects, which include anti-inflammatory actions, antiplatelet aggregation, and improved plasma lipid prolife. This review provides a short summary of the most recent research on DPA.. In this review, we report on the latest association data as well as data generated from in-vitro and in-vivo studies on DPA and cardiovascular health, mental health, inflammation, and cancer. We also report on the newly identified DPA metabolites and their effects on exacerbation of inflammation in animal models.. Although there is a growing body of evidence supporting DPA's role as an important bioactive fatty acid, there is a need for more 'cause and effect studies', clinical trials and studies which can reveal whether DPA plays separate roles to those identified for eicosapentaenoic acid and docosahexaenoic acid.

Topics: Animals; Disease Models, Animal; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Humans; Inflammation; Lipid Metabolism; Mental Health; Neoplasms

Topics: Arachidonic Acid; Atherosclerosis; Biological Evolution; Brain; Cardiovascular Diseases; Diet; Dietary Fats; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Gene Expression; Gene Expression Regulation; Genetic Variation; Humans; Inflammation; Linoleic Acid; Nutrition Policy; Nutritional Requirements; Trans Fatty Acids

Background Peripheral artery disease (PAD) is an advanced form of atherosclerosis characterized by chronic inflammation. Resolution of inflammation is a highly coordinated process driven by specialized pro-resolving lipid mediators endogenously derived from omega-3 fatty acids. We investigated the impact of a short-course, oral, enriched marine oil supplement on leukocyte phenotype and biochemical mediators in patients with symptomatic PAD and healthy volunteers. Methods and Results This was a prospective, open-label study of 5-day oral administration of an enriched marine oil supplement, assessing 3 escalating doses in 10 healthy volunteers and 10 patients with PAD. Over the course of the study, there was a significant increase in the plasma level of several lipid mediator families, total specialized pro-resolving lipid mediators, and specialized pro-resolving lipid mediator:prostaglandin ratio. Supplementation was associated with an increase in phagocytic activity of peripheral blood monocytes and neutrophils. Circulating monocyte phenotyping demonstrated reduced expression of multiple proinflammatory markers (cluster of differentiation 18, 163, 54, and 36, and chemokine receptor 2). Similarly, transcriptional profiling of monocyte-derived macrophages displayed polarization toward a reparative phenotype postsupplementation. The most notable cellular and biochemical changes over the study occurred in patients with PAD. There were strong correlations between integrated biochemical measures of lipid mediators (specialized pro-resolving lipid mediators:prostaglandin ratio) and phenotypic changes in circulating leukocytes in both healthy individuals and patients with PAD. Conclusions These data suggest that short-term enriched marine oil supplementation dramatically remodels downstream lipid mediator pathways and induces a less inflammatory and more pro-resolution phenotype in circulating leukocytes and monocyte-derived macrophages. Further studies are required to determine the potential clinical relevance of these findings in patients with PAD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02719665.

Topics: Adult; Aged; Biomarkers; Dietary Supplements; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Gene Expression; Healthy Volunteers; Humans; Inflammation; Lipid Metabolism; Male; Middle Aged; Monocytes; Peripheral Arterial Disease; Phagocytosis; Pilot Projects; Prospective Studies; Secondary Prevention

7S,15R-Dihydroxy-16S,17S-epoxy-docosapentaenoic acid (diHEP-DPA) and 7S,15R,16S,17S-tetrahydroxy-docosapentaenoic acid (TH-DPA) are two novel lipid mediators derived from docosahexaenoic acid (DHA) that we previously synthesized via combined enzymatic and chemical reactions. In the present study, we investigated the effects of these compounds on disturbances in lipid metabolism and liver inflammation induced by a high fat diet (HFD) in mice. Male BALB/c mice were randomly divided into four groups (n = 10/group): controls, HFD only, HFD + diHEP-DPA, and HFD + TH-DPA. Mice in HFD + diHEP-DPA and HFD + TH-DPA groups were orally administered 20 μg/kg of diHEP-DPA or TH-DPA, respectively. Measurements of adipose accumulation and liver inflammation showed that both diHEP-DPA and TH-DPA decreased adipose tissue mass and liver color depth, as well as total cholesterol, triglycerides, and low-density lipoprotein-cholesterol in the serum of HFD-fed mice compared with mice in the HFD-only group, while elevating high-density lipoprotein-cholesterol. Both of them also decreased hepatic expression of genes encoding lipid synthesis-related proteins (PPARγ, SIRT1, SREBP-1c and FASN) and increased the expression of genes encoding proteins involved in lipid degradation (PPARα and CPT-1) in the liver. Western blotting and quantitative RT-PCR confirmed that diHEP-DPA or TH-DPA administration modulated the expression of inflammation-related genes (TNF-α and IL-6) and inhibited activation of the NF-κB signaling pathway in livers of HFD-fed mice. Taken together, our data indicate that diHEP-DPA and TH-DPA ameliorate liver inflammation and inhibit HFD-induced obesity in mice.

Topics: Adipose Tissue; Animals; Cholesterol; Diet, High-Fat; Docosahexaenoic Acids; Fatty Acids, Unsaturated; Inflammation; Lipid Metabolism; Lipogenesis; Lipoxygenase; Liver; Male; Mice; Mice, Inbred BALB C; Obesity; Triglycerides

Ulcerative colitis (UC) is difficult to eradicate as it leads to chronic inflammation in the digestive tract due to immune system malfunction. The present study demonstrated the protective effect of 7S,15R‑dihydroxy‑16S,17S‑epoxy‑docosapentaenoic acid (diHEP‑DPA), which had been previously synthesized, on a dextran sulfate sodium (DSS)‑induced BALB/c mouse model of UC. UC was induced with 4% DSS drinking water for 7 days. Initially, the anti‑inflammatory effect of diHEP‑DPA was confirmed by demonstrating that lipopolysaccharide‑stimulated THP1 cells treated with diHEP‑DPA decreased IL‑6, TNF‑α and nitrite levels by fluorescence‑activated cell sorting (FACS) and Griess reagent kit. The results indicated that the administration of diHEP‑DPA at 20 µg/kg significantly reduced the severity of colitis, as determined by hematoxylin and eosin staining. The levels of TNF‑α, IL‑6 and IL‑1β in the colon tissue and serum were significantly reduced in the diHEP‑DPA + DSS‑treated group compared with in the control group, as determined by FACS and ELISA kit. It was also observed that diHEP‑DPA decreased myeloperoxidase (MPO) and nitrite levels in the colon tissues of diHEP‑DPA + DSS‑treated mice, as indicated using commercial MPO and nitric oxide kits. The diHEP‑DPA+DSS‑treated mice also exhibited decreased expression levels of phosporylated (p)‑inhibitor κB protein, p‑p65 and inducible nitric oxide synthase in the colon tissue by inhibiting inflammation, which were measured by reverse transcription‑quantitative PCR and weatern blot analysis. Overall, the present study demonstrated the protective effect of diHEP‑DPA against a severe colitis condition

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Fatty Acids, Unsaturated; Inflammation; Interleukin-6; Mice; Mice, Inbred BALB C; NF-kappa B; Nitrites; Tumor Necrosis Factor-alpha

Topics: Animals; Anti-Inflammatory Agents; Docosahexaenoic Acids; Fatty Acids, Unsaturated; Humans; Inflammation; Macrophages; Neutrophils; Quantum Theory; Receptors, G-Protein-Coupled; Stereoisomerism

Disturbances in onset and resolution of inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. Dietary polyunsaturated fatty acids (PUFAs) can be converted into lipid mediators here collectively named oxylipins. These include classical eicosanoids, but also pro-resolving mediators. A balanced production of pro-inflammatory and pro-resolving oxylipins is of importance for adequate inflammatory responses and subsequent return to homeostasis.. Here we investigated if PUFA metabolism is disturbed in COPD patients.. Free PUFA and oxylipin levels were measured in induced sputum samples from the Bergen COPD cohort and COPD exacerbation study using liquid chromatography-mass spectrometry. Additionally, effects of whole cigarette smoke on PUFA metabolism in air-liquid interface cultures of primary bronchial epithelial cells were assessed.. Significantly lower levels of free alpha-linolenic acid, linoleic acid and eicosapentaenoic acid (EPA) were detected in sputum from stable COPD patients compared to controls. During acute exacerbation (AE), levels of free arachidonic acid and docosapentaenoic acid were higher than in stable COPD patients. Furthermore, levels of omega-3 EPA- and docosahexaenoic acid-derived oxylipins were lower in sputum from stable COPD patients compared to controls. Cyclooxygenase-2-converted mediators were mostly increased during AE. In vitro studies additionally showed that cigarette smoke exposure may also directly contribute to altered epithelial PUFA metabolism, and indirectly by causing airway epithelial remodelling.. Our findings show significant differences in PUFA metabolism in COPD patients compared to controls, further changed during AE. Airway epithelial remodelling may contribute to these changes. These findings provide new insight in impaired inflammatory resolution in COPD.

Topics: alpha-Linolenic Acid; Arachidonic Acid; Cigarette Smoking; Diet; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Humans; Inflammation; Male; Middle Aged; Oxylipins; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa; Smokers; Sputum

The anti-inflammatory profile of DPA was investigated via a dextran sulphate sodium (DSS)-induced colitis model, and was also compared with those of EPA and DHA. The results showed that DPA could significantly reduce (stronger than EPA and DHA) the disease activity index score, macroscopic appearance score, colon shortening, histological assessment, and myeloperoxidase accumulation in the colon. In addition, DPA also inhibited the abnormal production and mRNA expression of pro-inflammatory cytokines, namely tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 and improved the production and expression of an anti-inflammatory cytokine, IL-10. Furthermore, the molecular mechanisms underlying these effects were also explored through the synthesis pathway of eicosanoids. DPA could inhibit the synthesis of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) more greatly while differences of cyclooxygenase (COX) and 5-lipoxidase (LOX) contents in these three groups were not significant. We ascribed these effects to the easier incorporation of DPA into inflammatory cells leading to the decrease in the substrate for the synthesis of pro-inflammatory eicosanoids (PGE2 and LTB4). Besides, DPA-derived mediators might also be involved.

Topics: Animals; Anti-Inflammatory Agents; Body Weight; Colitis, Ulcerative; Colon; Cytokines; Dextran Sulfate; Dinoprostone; Disease Models, Animal; Fatty Acids, Unsaturated; Inflammation; Interleukin-1beta; Leukotriene B4; Lipoxygenase; Male; Mice; Plant Extracts; Prostaglandin-Endoperoxide Synthases; RNA, Messenger; Tumor Necrosis Factor-alpha

Diurnal mechanisms are central to regulating host responses. Recent studies uncovered a novel family of mediators termed as specialized proresolving mediators that terminate inflammation without interfering with the immune response.. Herein, we investigated the diurnal regulation of specialized proresolving mediators in humans and their role in controlling peripheral blood leukocyte and platelet activation.. Using lipid mediator profiling and healthy volunteers, we found that plasma concentrations of n-3 docosapentaenoic acid-derived D-series resolvins (RvD. These results demonstrate that peripheral blood RvD

Topics: Adenosine; Animals; Blood Platelets; Circadian Rhythm; Fatty Acids, Unsaturated; Humans; Inflammation; Leukocytes; Lipoxygenase; Mice; Myocardial Infarction; Thromboxane B2

Specialized pro-resolving lipid mediators are biosynthesized during the resolution phase of acute inflammation from n-3 polyunsaturated fatty acids. Recently, the isolation and identification of the four novel mediators denoted 13-series resolvins, namely, RvT1 (1), RvT2 (2), RvT3 (3) and RvT4 (4), were reported, which showed potent bioactions characteristic for specialized pro-resolving lipid mediators. Herein, based on results from LC/MS-MS metabololipidomics and the stereoselective synthesis of 13(R)-hydroxy-7Z,10Z,13R,14E,16Z,19Z docosapentaenoic acid (13R-HDPA, 5), we provide direct evidence that the four novel mediators 1-4 are all biosynthesized from the pivotal intermediate 5. The UV and LC/MS-MS results from synthetic 13R-HDPA (5) matched those from endogenously and biosynthetically produced material obtained from in vivo infectious exudates, endothelial cells, and human recombinant COX-2 enzyme. Stereochemically pure 5 was obtained with the use of a chiral pool starting material that installed the configuration at the C-13 atom as R. Two stereoselective Z-Wittig reactions and two Z-selective reductions of internal alkynes afforded the geometrically pure alkene moieties in 5. Incubation of 5 with isolated human neutrophils gave all four RvTs. The results presented herein provide new knowledge on the biosynthetic pathways and the enzymatic origin of RvTs 1-4.

Topics: Animals; Chromatography, Liquid; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Humans; Inflammation; Inflammation Mediators; Macrophages; Molecular Structure; Neutrophils; Nuclear Magnetic Resonance, Biomolecular; Stereoisomerism

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and bones. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines and eicosanoids involved in RA pathogenesis. The aim of this study was to determine the therapeutic potential of ω3 monoglyceride (MAG-ω3) compounds in an in vivo rat model of RA induced by Complete Freund's Adjuvant (CFA).. CFA rats were untreated or treated per os with three specific compounds, namely, MAG-docosahexaenoic acid (MAG-DHA), MAG-eicosapentaenoic acid (MAG-EPA) and MAG-docosapentaenoic acid (MAG-DPA). Morphological and histological analyses, as well as pro-inflammatory marker levels were determined following MAG-ω3 treatments.. Morphological and histological analyses revealed that MAG-EPA and MAG-DPA exhibited strong activity in reducing the progression and severity of arthritic disease in CFA rats. Following MAG-EPA and MAG-DPA treatments, plasma levels of the pro-inflammatory cytokines; interleukin 17A (IL-17A), IL-1β, IL-6 and tumor necrosis factor α (TNFα) were markedly lower when compared to CFA-untreated rats. Results also revealed a decreased activation of p38 mitogen-activated protein kinases (p38 MAPK) and nuclear factor-kappa B (NFκB) pathways correlated with a reduced expression of TNFα, cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2) and MMP-9 in paw homogenates derived from MAG-EPA and MAG-DPA-treated rats. Of interest, the combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in CFA rats.. Altogether, the present data suggest that MAG-EPA, without vitamin E, represents a new potential therapeutic strategy for resolving inflammation in arthritis.

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Blotting, Western; Cyclooxygenase 2; Docosahexaenoic Acids; Eicosapentaenoic Acid; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Unsaturated; Female; Inflammation; Interleukin-17; Interleukin-1beta; Interleukin-6; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Monoglycerides; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Rats, Inbred Lew; Severity of Illness Index; Tumor Necrosis Factor-alpha

n-3 Polyunsaturated fatty acids (n-3 PUFA) have been shown to reduce inflammation and proliferation of pulmonary artery smooth muscle cells under pathophysiological conditions. However, the anti-inflammatory effect of the newly synthesized docosapentaenoic acid monoacylglyceride (MAG-DPA) on key signaling pathways in pulmonary hypertension (PH) pathogenesis has yet to be assessed. The aim of the present study was to determine the effects of MAG-DPA on pulmonary inflammation and remodeling occurring in a rat model of PH, induced by a single injection of monocrotaline (MCT: 60 mg/kg). Our results demonstrate that MAG-DPA treatment for 3 wk following MCT injection resulted in a significant improvement of right ventricular hypertrophy (RVH) and a reduction in Fulton's Index (FI). Morphometric analyses revealed that the wall thickness of pulmonary arterioles was significantly lower in MCT + MAG-DPA-treated rats compared with controls. This result was further correlated with a decrease in Ki-67 immunostaining. Following MAG-DPA treatments, lipid analysis showed a consistent increase in DPA together with lower levels of arachidonic acid (AA), as measured in blood and tissue samples. Furthermore, in MCT-treated rats, oral administration of MAG-DPA decreased NF-κB and p38 MAPK activation, leading to a reduction in MMP-2, MMP-9, and VEGF expression levels in lung tissue homogenates. Altogether, these data provide new evidence regarding the mode of action of MAG-DPA in the prevention of pulmonary hypertension induced by MCT.

Topics: Animals; Arachidonic Acid; Arterioles; Fatty Acids, Unsaturated; Hypertension, Pulmonary; Inflammation; Lipid Metabolism; Lung; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Monoglycerides; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Rats; Rats, Wistar; Vascular Endothelial Growth Factor A; Vascular Remodeling

We examined the prevalence of elevated plasma high-sensitivity C-reactive protein (hs-CRP) concentrations and associations with red blood cell (RBC) long-chain n-3 polyunsaturated fatty acids (LCn-3PUFA) in the James Bay Cree population from the province of Quebec (Canada).. A total of 744 Cree adults (18-91 years) from seven communities of Eastern James Bay were included in these cross-sectional analyses. Associations between RBC LCn-3PUFA and proinflammatory markers (hs-CRP, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)) were assessed by using multivariate general linear models with adjustment for sex, age and waist circumference. An arbitrary inflammation score was defined based on the sum of the quartiles of hs-CRP, IL-6 and TNF-α concentrations (range=3-12).. Elevated hs-CRP concentrations (>3 mg/l) were present in 46.9% (95% confidence interval (CI) 43.3-50.5) of the James Bay Cree population. RBC docosapentaenoic acid (DPAn-3; C22:5n-3) was inversely associated with hs-CRP, TNF-α and the inflammation score (all P trend<0.02), whereas eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) in RBC were not associated with inflammation (all P trend>0.18). Among participants with RBC DPAn-3 levels above the median of the population, odds ratio of having an elevated inflammation score (≥9) was 0.67 (95% CI, 0.48-0.93) compared with participants below the median.. RESULTS indicate that low-grade systemic inflammation is highly prevalent and that higher RBC DPAn-3 levels are associated with a lower risk of systemic inflammation in the James Bay Cree population.

Topics: Adult; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Docosahexaenoic Acids; Eicosapentaenoic Acid; Erythrocytes; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Humans; Indians, North American; Inflammation; Interleukin-6; Male; Prevalence; Quebec; Tumor Necrosis Factor-alpha

Resolution of inflammation is now held to be an active process where autacoids promote homeostasis. Using functional-metabololipidomics and in vivo systems, herein we report that endogenous n-3 docosapentaenoic (DPA) acid is converted during inflammation-resolution in mice and by human leukocytes to novel n-3 products congenerous to D-series resolvins (Rv), protectins (PD) and maresins (MaR), termed specialized pro-resolving mediators (SPM). The new n-3 DPA structures include 7,8,17-trihydroxy-9,11,13,15E,19Z-docosapentaenoic acid (RvD1(n-3 DPA)), 7,14-dihydroxy-8,10,12,16Z,19Z-docosapentaenoic acid (MaR1(n-3 DPA)) and related bioactive products. Each n-3 DPA-SPM displayed protective actions from second organ injury and reduced systemic inflammation in ischemia-reperfusion. The n-3 DPA-SPM, including RvD1(n-3 DPA) and MaR1(n-3 DPA), each exerted potent leukocyte directed actions in vivo. With human leukocytes each n-3 DPA-SPM reduced neutrophil chemotaxis, adhesion and enhanced macrophage phagocytosis. Together, these findings demonstrate that n-3 DPA is converted to novel immunoresolvents with actions comparable to resolvins and are likely produced in humans when n-3 DPA is elevated.

Topics: Animals; CD59 Antigens; Cell Adhesion; Cells, Cultured; Chemotaxis; Docosahexaenoic Acids; Endothelium, Vascular; Fatty Acids, Unsaturated; Humans; Inflammation; Inflammation Mediators; Leukocytes; Lipids; Macrophages; Metabolomics; Mice; Neutrophils; Peritonitis; Phagocytosis; Reperfusion Injury

Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and α linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders.. The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes.. Supplementation with several EO/BO combinations increased circulating 20-22 carbon (20-22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by >50% and in stimulated neutrophils by >35%.. This study shows that dietary supplementation with BO/EO alters 20-22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation.

Topics: 8,11,14-Eicosatrienoic Acid; Adolescent; Adult; alpha-Linolenic Acid; Asthma; Cells, Cultured; Dietary Supplements; Echium; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Inflammation; Leukocytes, Mononuclear; Leukotrienes; Male; Middle Aged; Plant Oils; Seeds

The anti-inflammatory activity associated with fish oil has been ascribed to the long-chain polyunsaturated fatty acids (LC-PUFA), predominantly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Here we examined the anti-inflammatory effects of two DHA-rich algal oils, which contain little EPA, and determined the contribution of the constituent fatty acids, particularly DHA and docosapentaenoic acid (DPAn-6). In vitro, lipopolysaccharide (LPS)-stimulated Interleukin-1 beta (IL-1beta) and Tumor Necrosis Factor-alpha (TNF-alpha) secretion in human peripheral blood mononuclear cells (PBMC) was inhibited with apparent relative potencies of DPAn-6 (most potent) > DHA > EPA. In addition, DPAn-6 decreased intracellular levels of cyclooxygenase-2 (COX-2) and was a potent inhibitor of pro-inflammatory prostaglandin E2 (PGE2) production. DHA/DPAn-6-rich DHA-S (DHA-S) algal oil was more effective at reducing edema in rats than DHA-rich DHA-T (DHA-T), suggesting that DPAn-6 has anti-inflammatory properties. Further in vivo analyses demonstrated that feeding DPAn-6 alone, provided as an ethyl ester, reduced paw edema to an extent approaching that of indomethacin and enhanced the anti-inflammatory activity of DHA when given in combination. Together, these results demonstrate that DPAn-6 has anti-inflammatory activity and enhances the effect of DHA in vitro and in vivo. Thus, DHA-S algal oil may have potential for use in anti-inflammatory applications.

Topics: Animals; Anti-Inflammatory Agents; Cells, Cultured; Disease Models, Animal; Docosahexaenoic Acids; Edema; Eicosapentaenoic Acid; Eukaryota; Fatty Acids, Unsaturated; Humans; Inflammation; Interleukin-1beta; Leukocytes, Mononuclear; Male; Oils; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

High sensitivity C-reactive protein (hs-CRP) is a marker of low-grade sustained inflammation. Omega-3 (n-3) fatty acids have anti-inflammatory properties and are associated with reduced cardiovascular disease (CVD) risk. The aim of this study was to investigate whether plasma n-3 fatty acid concentration is related to hs-CRP concentration. A total of 124 free-living adults, were divided into tertiles of plasma hs-CRP (<1.0, 1.0-3.0 and >3.0 mg/l). Body composition and anthropometric measurements were recorded. Hs-CRP was analysed using immunoassays and fatty acids were measured by gas chromatography. Plasma hs-CRP concentration was negatively correlated with total n-3 fatty acids (P=0.05), eicosapentaenoic acid (EPA; P=0.002) and docosapentaenoic acid (DPA; P=0.01). The highest hs-CRP tertile (>3.0 mg/l) had significantly lower concentrations of total n-3 fatty acids, EPA and DPA, when compared with the other tertiles (P<0.05). This study provides evidence that in healthy individuals, plasma n-3 fatty acid concentration is inversely related to hs-CRP concentration, a surrogate marker of CVD risk.

Topics: Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Humans; Inflammation; Male; Middle Aged

Alpha-linolenic acid (ALA) reduces cardiovascular disease (CVD) risk, possibly by favorably changing vascular inflammation and endothelial dysfunction. Inflammatory markers and lipids and lipoproteins were assessed in hypercholesterolemic subjects (n = 23) fed 2 diets low in saturated fat and cholesterol, and high in PUFA varying in ALA (ALA Diet) and linoleic acid (LA Diet) compared with an average American diet (AAD). The ALA Diet provided 17% energy from PUFA (10.5% LA; 6.5% ALA); the LA Diet provided 16.4% energy from PUFA (12.6% LA; 3.6% ALA); and the AAD provided 8.7% energy from PUFA (7.7% LA; 0.8% ALA). The ALA Diet decreased C-reactive protein (CRP, P < 0.01), whereas the LA Diet tended to decrease CRP (P = 0.08). Although the 2 high-PUFA diets similarly decreased intercellular cell adhesion molecule-1 vs. AAD (-19.1% by the ALA Diet, P < 0.01; -11.0% by the LA Diet, P < 0.01), the ALA Diet decreased vascular cell adhesion molecule-1 (VCAM-1, -15.6% vs. -3.1%, P < 0.01) and E-selectin (-14.6% vs. -8.1%, P < 0.01) more than the LA Diet. Changes in CRP and VCAM-1 were inversely associated with changes in serum eicosapentaenoic acid (EPA) (r = -0.496, P = 0.016; r = -0.418, P = 0.047), or EPA plus docosapentaenoic acid (r = -0.409, P = 0.053; r = -0.357, P = 0.091) after subjects consumed the ALA Diet. The 2 high-PUFA diets decreased serum total cholesterol, LDL cholesterol and triglycerides similarly (P < 0.05); the ALA Diet decreased HDL cholesterol and apolipoprotein AI compared with the AAD (P < 0.05). ALA appears to decrease CVD risk by inhibiting vascular inflammation and endothelial activation beyond its lipid-lowering effects.

Topics: Adult; Aged; alpha-Linolenic Acid; Apolipoprotein A-I; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, Dietary; Cholesterol, HDL; Diet; Diet, Fat-Restricted; Dietary Fats; E-Selectin; Eicosapentaenoic Acid; Energy Intake; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Humans; Hypercholesterolemia; Inflammation; Lipids; Male; Middle Aged; Risk Factors; Vascular Cell Adhesion Molecule-1