ArticleLiterature Review

Omega-3 fatty acids and inflammatory processes: From molecules to man

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Abstract

Inappropriate, excessive or uncontrolled inflammation contributes to a range of human diseases. Inflammation involves a multitude of cell types, chemical mediators and interactions. The present article will describe nutritional and metabolic aspects of omega-6 (n-6) and omega-3 (n-3) fatty acids and explain the roles of bioactive members of those fatty acid families in inflammatory processes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are capable of partly inhibiting many aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid and production of pro-inflammatory cytokines. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid, and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of EPA and DHA include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor κB so reducing expression of inflammatory genes and activation of the anti-inflammatory transcription factor peroxisome proliferator-activated receptor γ. Animal experiments demonstrate benefit from EPA and DHA in a range of models of inflammatory conditions. Human trials demonstrate benefit of oral n-3 fatty acids in rheumatoid arthritis and in stabilizing advanced atherosclerotic plaques. Intravenous n-3 fatty acids may have benefits in critically ill patients through reduced inflammation. The anti-inflammatory and inflammation resolving actions of EPA, DHA and their derivatives are of clinical relevance.

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... Les AGPI n-3 ainsi que leurs métabolites régulent aussi l'expression d'un certain nombre de gènes par l'intermédiaire de facteurs de transcription, tels que les PPARs, SREBP-1C (« Sterol Regulatory Element Binding Protein 1C ») (Dossi et al., 2014), HNF4 (« Hepatic nuclear factor 4 »), RXR et LXR (« Liver X receptor ») (Calder, 2017;Guesnet et al., 2005). (Oh et al., 2010). ...
... Les AGPI n-3 jouent un rôle important dans la santé de l'Homme (Calder, 2017;Simopoulos, 2016). Les apports en AGPI n-3 d'origine marine, EPA et DHA, sur modèles murins ont démontré leurs effets sur le profil lipidique avec un effet hypo-triglycéridémiant Chez des patients atteints de DT2, une diminution des TG circulants et une augmentation des HDL (« High density lipoprotein ») ont été observées à la suite d'une supplémentation en DHA, contrairement à la supplémentation en EPA où aucun effet n'a été rapporté (4 g par jour pendant 6 semaines). ...
... Cette réponse inflammatoire n'est pas due à une amélioration de l'intégrité de la barrière intestinale, ce qui nous permet d'émettre l'hypothèse que les AGPI n-3 se sont incorporés dans les membranes de cellules épithéliales et à la suite de l'inflammation ont permis la production de médiateurs pro-résolution de l'inflammation, les SPMs. Les SPMs via leur action sur PPARγ permettraient l'inhibition de la voie NF-kB, améliorant ainsi la réponse inflammatoire (Calder, 2017(Calder, , 2020. Nous avons montré une modulation du microbiote intestinal associé à la muqueuse colique chez les souris du groupe LS-E, et plus précisément de la diversité β, ainsi qu'une tendance à l'augmentation de la diversité α. ...
Thesis
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La prévention primaire et secondaire des pathologies inflammatoires chroniques telles que l’obésité et la maladie de Crohn (MC) reposent majoritairement sur des mesures hygiéno-diététiques incluant l’activité physique et la nutrition. Dans le cadre de ce travail de thèse, l’objectif principal était d’étudier l’influence de modalités d’exercice - exercice imposé de type intermittent de haute intensité (HIIT) ou activité de roue spontanée - associé à un apport en lin, riche en acides gras polyinsaturés (AGPI) n-3, sur les interrelations « composition corporelle – inflammation – microbiote intestinal » dans un contexte de pathologies inflammatoires chroniques (obésité, MC) sur modèles murins. Le deuxième objectif était d’étudier spécifiquement deux formes de lin, à travers la graine ou l’huile, afin de déterminer si la matrice de la graine de lin extrudée pouvait avoir des effets qui lui sont propres. Nos résultats indiquent qu’un programme de type HIIT est efficace pour prévenir la prise de poids et de masse grasse, et que le lin, indépendamment de sa forme, diminue l’inflammation. Nos travaux ont également montré un effet majeur du HIIT et de la graine de lin extrudée (TRADILIN, Valorex®) sur la modulation de la composition du microbiote intestinal associé à la muqueuse. Certaines de ces variations étaient corrélées aux modulations de la composition corporelle mais non à l’inflammation. Nos travaux ont montré spécifiquement un effet synergique du HIIT et de l’huile de lin sur l’abondance d’Oscillospira spp. et sur la conversion de l’acide α-linolénique en acide docosahexaénoïque. En conclusion, nos résultats montrent qu’un apport en lin, et particulièrement sous forme de graines extrudées, associé à une activité physique imposée et suffisamment intense, pourraient être efficace dans la prévention et/ou la prise en charge des pathologies inflammatoires chroniques telles que l’obésité et la MC. Les interrelations « composition corporelle – inflammation – microbiote intestinal », restent toutefois à approfondir et les mécanismes sous-jacents à explorer.
... 39 In addition, EPA and DHA are related to the decrease in the production of cytokines, T cell reactivity, PGE2 metabolites, thromboxane A2 (linked to platelet aggregation and vasoconstriction), leukotriene B4 (inflammation and potent inducer of leukocytes, lymphocytes, macrophages, endothelial cells chemotaxis, and adherence) and IL-6 and the increase of thromboxane A3 (weak platelet aggregation and vasoconstrictor), prostacyclin PGI3 and PGI2 (vasodilators and inhibitors of platelet aggregation), leukotriene B5 (low inflammation and chemotactic agent). [40][41][42][43][44] Thus, EPA and DHA-rich diets or supplement intake have central role correlated with decreasing and preventing incidence of RA and UC effects on human subjects. [44][45][46][47][48][49][50] ...
... [40][41][42][43][44] Thus, EPA and DHA-rich diets or supplement intake have central role correlated with decreasing and preventing incidence of RA and UC effects on human subjects. [44][45][46][47][48][49][50] ...
... 134 Prebiotics are considered food products or by-products that promote the growth and maintenance of a healthy and diverse gut microbiome capable of producing higher levels of SCFAs metabolites, especially butyrate, which has the capacity of inhibiting inflammatory pathways by suppressing NF-jB activity and the expression of IL-1, IL-12, and TNF-a (proinflammatory cytokines), inducing mucin synthesis and in this way protecting the intestinal mucosa, and decreasing the bacterial influx from the intestinal lumen to the bloodstream by improving the tight junctions on intestine epithelial cells. 29,44,[132][133][134][135][136][137][138] One of the prebiotics we highlight is omega-3 fatty acids, well-studied by several researchers in several experimental and clinical studies. Results have shown their gut microbiota modulation property favoring butyrate producers and antiinflammatory properties for being precursors of EPA and DHA-derived eicosanoids, resolvins, and protectins, driving the inflammatory process to its control and resolution and avoiding tissue damage. ...
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The aim of this article was to review experimental and clinical studies regarding the use of omega-3 fatty acids on the prevention and control of chronic inflammatory diseases with autoimmune background through the gut microbiota modulation. For this, natural omega-3 sources are presented emphasizing the importance of a healthy diet for the body's homeostasis and the enzymatic processes that these fatty acids go through once inside the body. The pathogenesis of ulcerative colitis and rheumatoid arthritis are revisited under the light of the gut microbiota dysbiosis approach and how those fatty acids are able to prevent and control these two pathological conditions that are responsible for the global chronic burden and functional disability and life-threatening comorbidities if not treated properly. As a matter of reflection, as we are living a pandemic crisis owing to COVID-19 infection, we present the potential of omega-3 in preventing a poor prognosis once they contribute to balancing the immune system modulation the inflammatory process.
... γ-Linolenic acid (18:3n-6) (derived from linoleic acid, an essential FA by Δ6-desaturase) can be elongated by the enzyme elongase 5 to dihomo-γ-linolenic acid (20:3n-6; DGLA)(147).Then, DGLA undergoes oxidative metabolism by cyclooxygenases and lipoxygenases to produce anti-inflammatory eicosanoids (prostaglandins of series 1 and leukotrienes of series 3)(148). Using the same series of enzymes as used to metabolize n-6 PUFAs, n-3 α-linolenic acid is converted into long-chain FA (LC-PUFA): eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3;DHA). ...
... These FA are capable, in one part, of inhibiting many aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 arachidonic acid and production of pro-inflammatory cytokines. In a second part, EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins(147). ...
Thesis
As the incidence of ovarian cancer (OC) and endometrial cancer (EC) is rising worldwide, prevention strategies are needed. However, few preventable factors have been identified. Thus, their identification and implementation are warranted. This thesis aimed to better understand the the role of nutrition particularly fatty acids (FA). Within the European EPIC cohort including ~ 300 000 women, we assessed the association between estimated dietary intakes of FA, circulating FA and OC risk. Both approaches convened that higher dietary intakes and circulating levels of industrial trans FA were associated with greater OC risk. A positive association was also detected for higher intakes of linoleic acid and α-linolenic acid originating mainly from deep frying fat. We conducted an EPIC study between dietary intakes of FA and EC risk where we found negative associations with γ-linolenic acid and α-linolenic acid intakes from plant sources. Such studies would be relevant in low-middle-income countries (LMICs), undergoing nutrition transition, characterized by the adoption of westernized diets. In this context, we assessed in a recent Lebanese cohort, the associations between serum FA and obesity, a risk factor for OC and EC. In this population, high markers of endogenous FA synthesis were positively correlated with adiposity. Our data suggest that eliminating industrial trans FA intake could reduce OC risk. The risk of EC may be decreased by adhering to a diet high in vegetables. Our study conducted in Lebanon could provide a baseline for future work aiming to study dietary factors and cancer risk in LMICs.
... Polyunsaturated fatty acids (PUFAs) are a type of essential fatty acids that cannot be synthesized by humans. It has been demonstrated that PUFAs are localized in cell membrane and involve in a large number of physiological functions, such as inflammation, blood sugar control, regulation of blood pressure, and cell signaling (8)(9)(10)(11). Based on the different position of the first double bond, PUFAs could be classified into two major classes: omega-3 and omega-6. Evidence from human and animal studies indicated that omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammation properties that showed some improvements in the rheumatic diseases (12)(13)(14). ...
... Omega -6 PUFAs have been demonstrated to play a crucial role in stimulating the growth of skin and hair, regulating lipid metabolism, and improving bone health (39)(40)(41). Additional evidence has highlighted the important roles of omega-6 in cytokine production and monocyte chemotaxis (9,42). However, as omega-3 and omega-6 compete for the same desaturation and elongation enzymes, the excessive intake of omega-6 causes an increased ratio of omega-6 to omega-3, and competes with benefits of omega-3, increasing the probability of CVD, cancers, and inflammatory diseases (43,44 of omega-6 (linoleic acid) positively correlated with systemic lupus activity measure (SLAM), and AT omega-6 (arachidonic acid) showed a positive association with the systemic lupus international collaborating clinics (SLICC) damage index (45). ...
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Background Accumulating evidence has demonstrated the associations of omega-3 or omega-6 polyunsaturated fatty acids (PUFAs) with the disease activity and inflammatory mediators of systemic lupus erythematosus (SLE), but the evidence of causal links of omega-3 or omega-6 PUFAs on the risk for SLE remains inconclusive. Objectives This study was conducted to evaluate the causal relationships between omega-3/omega-6 PUFAs and SLE by performing the Mendelian randomization (MR) analysis. Methods Genome-wide significant single-nucleotide polymorphisms (SNPs) were obtained from genome-wide association studies (GWASs) of circulating omega-3/omega-6 levels ( n = up to 13,544) and GWAS meta-analyses of SLE ( n = 14,267), respectively. The bidirectional two-sample MR (TSMR) analysis was conducted to infer the causality. Results The inverse-variance weighted (IVW) method revealed that genetically determined per SD increase in omega-3 levels were causally associated with an increased risk for SLE (odds ratios [ OR s] = 1.49, 95% CI : 1.07, 2.08, p = 0.021), but no causal effect of omega-6 on the risk SLE was observed (IVW OR = 1.06, 95% CI : 0.72, 1.57, p = 0.759). In addition, there were no significantly causal associations in genetic predisposition to SLE with the changes of omega-3 and omega-6 levels, respectively (IVW beta for omega-3: 0.007, 95% CI : −0.006, 0.022, p = 0.299; IVW beta for omega-6: −0.008, 95% CI : −0.023, 0.006, p = 0.255). Conclusion The present study revealed the possible causal role of omega-3 on increasing the risk for SLE, it could be the potential implications for dietary recommendations.
... This suggests that the reduced intestinal barrier function seen in the Atlantic salmon, at least in part, is a result of an increase in the pro-inflammatory FA, ARA. Yet another support for the correlation between long chain omega-3 FA and reduced inflammation in mammals is that increased levels of DHA and EPA decreases ARA in mammals (Calder, 2017). This may reduce a proinflammatory reaction through decreased production of potent eicosanoids, and possibly also through reduced production of pro-inflammatory cytokines, also known to induce intestinal barrier dysfunction (Calder, 2017). ...
... Yet another support for the correlation between long chain omega-3 FA and reduced inflammation in mammals is that increased levels of DHA and EPA decreases ARA in mammals (Calder, 2017). This may reduce a proinflammatory reaction through decreased production of potent eicosanoids, and possibly also through reduced production of pro-inflammatory cytokines, also known to induce intestinal barrier dysfunction (Calder, 2017). Further studies are however needed to elucidate if the observed intestinal barrier dysfunction of Atlantic salmon fed low, 0.5%, omega-3 levels also is mediated by increased pro-inflammatory reactions as a result of increased eicosanoid production from ARA. ...
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Due to a limited access to marine raw materials from capture fisheries, Atlantic salmon feeds are currently based on mainly plant ingredients (75%) while only 25% come from traditional marine ingredients including marine fish meal and fish oil. Thus, current feeds contain less of the essential omega-3 fatty acids. The aim of the study was to assess the impact of different omega-3 levels in fish feed on intestinal barrier and transporting functions of Atlantic salmon freshwater and seawater smolts. Atlantic salmon were fed three levels of omega-3 (2, 1 and 0.5%) and fish performance was followed through smoltification and the subsequent seawater acclimation. Intestinal barrier and transporting functions were assessed using Ussing chamber methodology and combined with transcript analysis of tight junction related proteins and ion transporters. A linear decrease in growth was observed with decreasing omega-3 levels. Low (0.5%) inclusion of omega-3 impaired the barrier function of the proximal intestine compared to 2% inclusion. Further, low levels of omega-3 decrease the transepithelial electrical potential across the epithelium indicating disturbed ion transport. It can be concluded that low dietary levels of omega-3 impair somatic growth and intestinal function of Atlantic salmon.
... Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are a class of PUFAs with the first unsaturated double bond between the third and fourth carbon atoms from the methyl end. ω-3 PUFAs have various effects on the cardiovascular system and can provide multiple health benefits for the cardiovascular system (1,2) via various mechanisms, such as reduction in blood lipids and inflammatory cell aggregation (3)(4)(5)(6)(7)(8)(9)(10), and the reduction of triglycerides in the blood is thought to be the main benefit (11). Multiple studies have investigated the association between ω-3 PUFAs supplementation and less coronary atherosclerotic "high-risk" plaque. ...
... (4) Death cases were excluded from endpoint assessment. (5) We included only studies that all the follow-up work completed to ensure the whole data was available. (6) The number of follow-up patients should not be <15, which means the data could be calculated by Cohen's d effect size. ...
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Background and PurposeMultiple guidelines suggest the ω-3 polyunsaturated fatty acids (ω-3 PUFAs) help to prevent major vascular events of coronary heart disease (CHD), but the data on large trials of ω-3 fatty acids are controversial. We reviewed the available evidence to determine the effect of ω-3 PUFAs on coronary atherosclerosis.Materials and Methods Literature were from online databases. Randomized controlled trials (RCTs) or observational studies were acceptable. Quantitative data synthesis was conducted using R version 4.1.2. Each outcome was calculated using standardized mean difference (SMD) in a random-effect model. Sensitivity analysis was conducted for each outcome. A total of 21 RCTs and 1 observational study with 2,277 participants were included.ResultsMeta-analysis indicated a benefit of ω-3 PUFAs on coronary atherosclerosis, namely, (1) ω-3 PUFAs can reduce the atherosclerotic plaque volume (SMD −0.18; 95% CI −0.31 to −0.05); (2) ω-3 PUFAs can help reduce the loss of the diameter of the narrowest segments of coronary arteries in patients with CHD (SMD 0.29; 95% CI, 0.05–0.53); (3) ω-3 PUFAs do not have significant effect on volume of lipid plaque in coronary arteries (SMD −1.18; 95% CI −2.95 to 0.58), volume of fiber plaque (SMD 0.26; 95% CI −0.81 to 1.33), and calcified plaque (SMD 0.17; 95% CI −0.55 to 0.89); and (4) ω-3 PUFAs had no significant effect on endothelial inflammatory factors in peripheral blood.Conclusions We confirmed that ω-3 PUFAs benefit patients with CHD by reducing the progression of coronary atherosclerosis. We indicated that the benefits were not caused by reducing endothelial inflammations of coronary arteries.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021285139, identifier: CRD42021285139.
... In an exploratory analysis restricted to MSM in this study we observed a negative correlation between vitamin E, zeaxanthin and fish consumption with Erysipelotrichaceae abundance and a positive correlation with meat. For the case of MSM with MEL we observed there is a negative correlation with fish and eicosapentaonic acid (EPA) w-3 fatty acids found in oily fish with anti-inflammatory action and is clinically relevant beneficial [37,38] and with the carotenoide zeanxanthin. MSM with WEL pattern showed a strong negative correlation of Erysipelotrichaceae with antioxidants intake like vitamin E, dietary fibre and fruit consumption. ...
... Importantly, we found differences in the inflammatory biomarkers D-dimmer and sTNFR2 among PWH according to the dietary pattern followed, with levels in MEL being much lower than in WEL. sTNFR2 is a proinflammatory cytokine that is used as a marker of atherogenesis and is increased in PWH despite effective ART [37], as well as in other pro-inflammatory diseases [39][40][41]. D-dimer is a marker of fibrin degradation and its levels are often increased in PWH and denote a pre-thrombotic state that may lead to clinical thrombosis [42]. ...
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While changes in microbiome composition have been associated with HIV, the effect of diet and its potential impact on inflammation remains unclear. Methods: Twenty-seven people living with HIV (PWH) on antiretroviral therapy (ART) were studied. A comprehensive dietary analysis was performed and two types of dietary patterns were determined. We explored the associations of each dietary pattern with gut microbiota and plasma inflammatory biomarkers. Results: We appreciated two dietary patterns, Mediterranean-like (MEL) and one Western-like (WEL). Compared to participants with the WEL pattern, participants with MEL pattern showed higher abundance of Lachnospira (p-value = 0.02) and lower levels of the inflammatory biomarkers D-dimer (p-value = 0.050) and soluble TNF-alpha receptor 2 (sTNFR2) (p-value = 0.049). Men who have sex with men (MSM) with MEL pattern had lower abundance of Erysipelotrichaceae (p-value < 0.001) and lower levels of D-dimer (p-value = 0.026) than MSM with WEL pattern. Conclusion: MEL pattern favours Lachnospira abundance, and protects against Erysipelotrichaceae abundance and higher levels of the inflammatory biomarkers D-dimer and sTNFR2, precursors of inflammatory processes in HIV-infected patients. Our study contributes to understanding the determinants of a healthier diet and its connections with gut microbiota and inflammation.
... The upregulation of eicosanoid synthesis depends on enzyme activation and increased expression of genes encoding enzymes. 65 EPA has been shown to inhibit ARA metabolism, 66 whereas DHA plays a primary role in decreasing the expression of adhesion molecules on macrophages and lymphocytes. 67 Eicosapentaenoic acid/docosahexaenoic acid supplementation Dietary sources of EPA and DHA primarily include flaxseed oil, walnuts, Chia seeds, and oily fish such as salmon, tuna, anchovies, sardines, and shellfish. ...
Article
A literature review to identify nutritional factors and the prevention and management of knee or hip osteoarthritis (OA) suggests that nutritional interventions offer some health benefits in OA through mechanisms such as weight loss, reduced inflammation, and antioxidant capacity. However, because data are limited with mixed results, high-quality evidence, including longitudinal studies and clinical trials, are needed to understand whether nutritional supplementation effectively prevents or manages OA. Therefore, healthcare professionals should consider promoting diets rich in fiber, including whole grains, fruit, vegetables, nuts, seeds, and legumes or dietary patterns such as the Mediterranean diet, to their patients to manage OA.
... We hypothesized that each intervention could specifically affect the mucosa-associated gut microbiota composition (α and β diversity) with more favorable adaptations in the HIIT + LO group [116]. It is known that n-3 PUFAs from natural sources or dietary supplements exert a beneficial effect on body composition and inflammation status [188,189], improve the intestinal barrier function [63] and integrity, and increase healthy bacterial communities [62,190]. By combining HIIT and LO, we hoped to induce an additive or even synergistic effect on the intestinal mucosa-associated microbiota that would promote body composition and metabolic profile changes. ...
Article
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The human gut microbiota is currently the focus of converging interest in many diseases and sports performance. This review presents gut microbiota as a real “orchestra conductor” in the host’s physio(patho)logy due to its implications in many aspects of health and disease. Reciprocally, gut microbiota composition and activity are influenced by many different factors, such as diet and physical activity. Literature data have shown that macro- and micro-nutrients influence gut microbiota composition. Cumulative data indicate that gut bacteria are sensitive to modulation by physical activity, as shown by studies using training and hypoactivity models. Sports performance studies have also presented interesting and promising results. Therefore, gut microbiota could be considered a “pivotal” organ for health and sports performance, leading to a new concept: the nutrition-microbiota-physical activity triad. The next challenge for the scientific and medical communities is to test this concept in clinical studies. The long-term aim is to find the best combination of the three elements of this triad to optimize treatments, delay disease onset, or enhance sports performance. The many possibilities offered by biotic supplementation and training modalities open different avenues for future research.
... Conversely, omega-3 polyunsaturated fatty acids (n-3 PUFA) obtained from fish and plant-based dietary sources have anti-inflammatory effects (58). The mechanisms of action for n-3 PUFA immunosuppressive effects may be via their interaction with T cell signalling, effects on the intestinal barrier and/or direct effects on pro-inflammatory cytokine production (59)(60)(61)(62). An in vitro model showed that stimulation of T84 intestinal epithelial cells with n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) restored the intestinal barrier integrity after impairment (63). ...
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Diet is an important lifestyle factor that is known to contribute in the development of human disease. It is well established that poor diet plays an active role in exacerbating metabolic diseases, such as obesity, diabetes and hypertension. Our understanding of how the immune system drives chronic inflammation and disease pathogenesis has evolved in recent years. However, the contribution of dietary factors to inflammatory conditions such as inflammatory bowel disease, multiple sclerosis and arthritis remain poorly defined. A western diet has been associated as pro-inflammatory, in contrast to traditional dietary patterns that are associated as being anti-inflammatory. This may be due to direct effects of nutrients on immune cell function. Diet may also affect the composition and function of gut microbiota, which consequently affects immunity. In animal models of inflammatory disease, diet may modulate inflammation in the gastrointestinal tract and in other peripheral sites. Despite limitations of animal models, there is now emerging evidence to show that anti-inflammatory effects of diet may translate to human gastrointestinal and inflammatory diseases. However, appropriately designed, larger clinical studies must be conducted to confirm the therapeutic benefit of dietary therapy.
... Olive oil, palm oil, coconut oil, avocado oil and peanut oil, on the other hand, can sustain far greater temperatures than others. Because, fats rich in monounsaturated fatty acids are more stable and resistant to peroxidation and oxidative stress than oils with a higher amount of polyunsaturated acids (Calder, 2017), it is critical to choose oils that are primarily made up of them. ...
Article
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Repeated use of frying oils can produce elements that degrade food quality and promote the creation of chemicals with negative nutritional consequences and potential health risks. During multiple frying cycles in French fries, the quality of edible oils (soybean oil, rice bran oil, sunflower oil, and palm olein) was assessed. Except for RBO (F: 0.37-0.56 %), FFA percent was discovered in the usual range in SBO, SnFO, and PO. PV was raised by repeated frying, but SnFO showed the most instability (2.38-30.96) meq O2/kg. RBO produced the most trans-fat (0.85-1.21 percent), but SnFO did not produce any. While vitamin A content decreased after three frying cycles, the PO used before retained higher vitamin A (16.29-14.61 mg/kg). However, no oil, even extracted oils, holds up to the quality requirement after three frying cycles. Bangladesh J. Sci. Ind. Res. 57(1), 49-60, 2022
... Omega-3 not only prevents cardiovascular diseases but also protects against mortality. 13 It also has anti-inflammatory 14 and anti-depressive 15 properties. ...
Article
This systematic review was conducted to investigate the effects of vitamin E and omega-3 used alone and in combination on the frequency and intensity of hot flushes (primary outcomes) and adverse effects (secondary outcome) in menopausal women. English and Persian databases were searched until March 18, 2021. The quality of the published papers was evaluated using Cochrane Handbook and the meta-analysis was conducted in RevMan 5.3. Heterogeneity was assessed using I2. In cases with substantial heterogeneity, a random effects model was used instead of a fixed effects model. A total of 387 papers were obtained from the databases. Finally, 10 papers with a sample size of 1100 participants entered the systematic review and a meta-analysis was conducted on nine of them. The results of the meta-analysis of two studies indicated that using vitamin E and omega-3 in combination significantly reduced the intensity of hot flushes compared to the placebo (mean difference (MD): -0.35; 95% CI: -0.48 to -0.21). The mean frequency (MD: -0.50; 95% CI: -1.58 to 0.58) and intensity (SMD: -0.61; 95% CI: -1.50 to 0.29) of hot flushes in the omega-3 group and the frequency of hot flushes (SMD: -0.21; 95% CI: -0.47 to 0.04) in the vitamin E group showed no significant differences with the placebo. No serious adverse effects were reported in the studies. Given the low number of RCTs, more clinical trials with larger sample size are required.
... It has been detected in various placental and fetal compartments including amniotic fluids, fetal membranes, cord blood, and neonatal gastric aspirates. 11,21,24,25,[28][29][30][31][32][33] Fusobacterium nucleatum is a heterogeneous species, with five recognized subspecies (ie, animalis, fusiforme, nucleatum, polymorphum, and vincentii). 22 Therefore, maintenance of good oral health throughout the gestation is recommended, rather than the "one-time deal". ...
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The link between oral health and adverse pregnancy outcomes has been suggested by numerous epidemiological studies. More recent studies indicate the relationship between severity of periodontal disease and adverse pregnancy outcomes. Two virulence mechanisms are proposed: direct invasion of oral microorganisms or their components into the fetal‐placenta unit and inflammatory mediators produced in the oral cavity affecting the fetal‐placenta unit. While interventional periodontal therapy still yielded contradictory results, animal studies suggest that maternal supplementation of omega‐3 fatty acids protects the fetus by suppressing inflammation as well as bacteria proliferation in the placenta. This article reviews the recent epidemiological, mechanistic, interventional, and therapeutic studies of oral health and adverse pregnancy outcomes.
... It was demonstrated that n-3 PUFA involved in the intestinal immune regulation and maintenance of intestinal homeostasis (Robertson et al., 2016;Costantini et al., 2017). In this research, Shannon index and PCoA analysis results showed that IOF of linseed oil increased the species diversity and modulated the intestinal microbial communities of embryos at E19. Calder and Philip (2017) also showed that dietary supplement of fish oil significantly affected the diversity of intestinal microorganism compared with sunflower seed oil. Results of this study showed that the dominant phyla of chicken embryos were Proteobacteria, Bacteroidetes, Actinobacteria, and Firmicutes, which was similar to the results of Akinyemi et al. (2020). ...
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This study aimed to investigate the effects of in ovo feeding (IOF) and dietary addition (DA) oils on growth, development and immune function of broiler chickens. In experiment 1, a total of 500 eggs were randomly assigned to 3 treatments: non-injected group (CON) with 100 eggs; soybean oil oinjected group (SO) with 200 eggs and linseed oil injected group (LO) with 200 eggs. Results showed that there were no detrimental effects of IOF of oils on embryonic development. In experiment 2, a two factor experimental design was adopted. After hatching, 120 chicks which came from each oil-injected group were divided into two treatments with 6 replicates, and chickens were fed soybean oil diet and linseed oil diet, respectively. The results showed that DA linseed oil increased final body weight (FBW) of broilers at d 21 post hatch, IOF of linseed oil decreased average daily feed intake (ADFI) and feed conversion ratio (FCR) of broilers from day 1 to 21 (P < 0.05), while the plasma leptin level of 21-day-old broilers was increased by IOF or DA linseed oil (P < 0.05). Main effect analysis showed that DA linseed oil increased the spleen index and mRNA expression of IFN-γ in spleen of broilers at 7 d of age (P < 0.05). IOF of linseed oil up-regulated the mRNA expression of IFN-γ in the spleen of chicks at 1 d and mRNA expression of IL-2 and IL-4 in spleen of broilers at 21 d (P < 0.05), and the interaction effect showed that IOF and DA linseed oil synergically increased the expression of IL-2 and IL-4 in spleen of broilers at 21 d. Compared with SO group, LO increased the Shannon index of hatching-day cecum microflora (P < 0.05). Principal co-ordinates analysis (PcoA) showed that LO group clearly separated from CON and SO groups. Finally, Spearman correlation analysis also manifested that Alkalicoccus was significantly correlated with spleen index and mRNA expression of IL-2, and Phreatobacter was significantly correlated with the mRNA expression of IL-2 and IFN-γ in spleen, Acinetobacter had a positive correlation with thymus index (P < 0.05). In conclusion, IOF of linseed oil reduced the ADFI and FCR of broilers and increased the species diversity and changed the structure of cecal microflora of chicken embryos at the 19th day of incubation (E19). Immune function of broilers spleen was also regulated by IOF and DA linseed oil.
... Inflammation is an important component associated with ovarian cancer and its tumor microenvironment [59]. Omega-3 FAs are intimately involved in regulating the inflammatory processes and modulating cell function [60]. EPA treatment inhibited the mRNA expression of inflammatory cytokines including IL-1β, IL-6, MCP-1, and TNF-α in both the CaOV3 ( Figure 9A) and SKOV3ip tumors ( Figure 9C), which was validated by similar decreased levels of these inflammatory cytokines in the serum from mice of both tumor models ( Figure 9B,D). ...
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Metformin is being actively repurposed for the treatment of gynecologic malignancies including ovarian cancer. We investigated if metformin induces analogous metabolic changes across ovarian cancer cells. Functional metabolic analysis showed metformin caused an immediate and sustained decrease in oxygen consumption while increasing glycolysis across A2780, C200, and SKOV3ip cell lines. Untargeted metabolomics showed metformin to have differential effects on glycolysis and TCA cycle metabolites, while consistent increased fatty acid oxidation intermediates were observed across the three cell lines. Metabolite set enrichment analysis showed alpha-linolenic/linoleic acid metabolism as being most upregulated. Downstream mediators of the alpha-linolenic/linoleic acid metabolism, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were abundant in all three cell lines. EPA was more effective in inhibiting SKOV3 and CaOV3 xenografts, which correlated with inhibition of inflammatory markers and indicated a role for EPA-derived specialized pro-resolving mediators such as Resolvin E1. Thus, modulation of the metabolism of omega-3 fatty acids and their anti-inflammatory signaling molecules appears to be one of the common mechanisms of metformin’s antitumor activity. The distinct metabolic signature of the tumors may indicate metformin response and aid the preclinical and clinical interpretation of metformin therapy in ovarian and other cancers.
... En cuanto a los ácidos grasos poliinsaturados omega-3 que incluyen el ácido α-linolénico (ALA), el ácido eicosapentaenoico (EPA) y el ácido docosahexaenoico (DHA) que junto a sus productos (prostaglandinas, leucotrienos, tromboxanos) otorgan un beneficio en la regulación de la inflamación al ser mediadores pro-resolución (Calder, 2017;Gutiérrez, Svahn & Johansson, 2019). Los ácidos grasos encontrados en fuentes de origen animal como pescados y mariscos como representantes y en las fuentes de origen vegetal como las nueces, semillas o aceite de lino, podrían modular el ambiente inflamatorio que genera el COVID-19, especialmente con estos últimos. ...
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Resumen: La enfermedad por coronavirus 2019 es una enfermedad infecciosa que se identificó por primera vez en la ciudad de Wuhan en China. Hasta la fecha, la obesidad sarcopénica y la desnutrición proteica-energética mantienen una estrecha asociación con la aparición de formas graves de COVID-19, por lo que la presente revisión se centra en la importancia de una alimentación y ejercicio físico adecuados con el objetivo de disminuir la severidad de las infecciones por COVID-19 y de qué forma estos confluyen para complementar tratamientos médicos. Un exceso de grasa corporal y la aparición de desnutrición, nos mantienen más vulnerables a contraer la enfermedad por coronavirus; una pandemia de gran magnitud que, para distintas organizaciones internacionales de salud, se encuentra vinculada a dos tópicos centrales: La nutrición y el ejercicio físico. El desarrollo y aplicación de nuevas intervenciones nutricionales y de ejercicio es requerida con urgencia con el objetivo de no solo reducir la obesidad, desnutrición y sarcopenia adquiridos durante la pandemia de la enfermedad por coronavirus sino también para brotes virales que posiblemente puedan acontecer a futuro. Abstract: Coronavirus disease 2019 is an infectious disease that was first identified in the city of Wuhan in China. To date, obesity and protein-energy malnutrition maintain a close association with the appearance of severe forms of COVID-19, so this review focuses on the importance of adequate nutrition and physical exercise to reduce the severity of COVID-19 infections and how they come together to complement medical treatments. An excess of body fat and the appearance of malnutrition, keep us more vulnerable to contracting the coronavirus disease; a pandemic of great magnitude that, for different international health organizations, is linked to two central topics: nutrition and physical exercise. The development and application of new nutritional and exercise interventions is urgently required with the aim of not only reducing obesity, malnutrition and sarcopenia acquired during the coronavirus disease pandemic but also for viral outbreaks that may possibly occur in the future.
... Previous studies have proposed that serum PUFAs levels in patients with rheumatic diseases were usually lower (42,43). w-3 Fatty acids have potential immunomodulatory and anti-inflammatory effects, which could inhibit inflammation by reducing the expression of cell surface molecules and adhesion molecules, inhibiting inflammatory factors, and affecting immune cell function (44,45). Furthermore, studies have reported that in mouse models, dietary w-3 fatty acids had been successfully used to reduce the severity of arthritis and atopic dermatitis by promoting the differentiation of CD4 + T cells into Tregs (41,46,47). ...
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Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, and the diagnosis is quite difficult due to the unavailability of reliable clinical markers. This study aimed to investigate the fecal metabolites in PsA by comparison with rheumatoid arthritis (RA), and to identify potential diagnostic biomarkers for PsA. The metabolic profiles of the fecal samples from 27 PsA and 29 RA patients and also 36 healthy controls (HCs) were performed on ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). And differentially altered metabolites were screened and assessed using multivariate analysis for exploring the potential biomarkers of PsA. The results showed that 154 fecal metabolites were significantly altered in PsA patients when compared with HCs, and 45 metabolites were different when compared with RA patients. A total of 14 common differential metabolites could be defined as candidate biomarkers. Furthermore, a support vector machines (SVM) model was performed to distinguish PsA from RA patients and HCs, and 5 fecal metabolites, namely, α/β-turmerone, glycerol 1-hexadecanoate, dihydrosphingosine, pantothenic acid and glutamine, were determined as biomarkers for PsA. Through the metabolic pathways analysis, we found that the abnormality of amino acid metabolism, bile acid metabolism and lipid metabolism might contribute to the occurrence and development of PsA. In summary, our research provided ideas for the early diagnosis and treatment of PsA by identifying fecal biomarkers and analyzing metabolic pathways.
... Omega-3 fish oils were prescribed most commonly for symptoms related to pain and inflammation (Table 4). 17,18 Omega-3 fatty acids may play a role in mitigating the debilitating effects of widespread pain as some research has found FM patients to have lower circulating levels of Eicosopentaenoic acid (EPA), 19 and increased neuroinflammation and systemic inflammation. 20 EPA and Docosahexaenoic acid appear to have the ability to inhibit or modulate specific aspects of inflammation, as well as give rise to anti-inflammatory and inflammation resolving mediators. ...
Article
Background: Fibromyalgia (FM) is characterized by chronic pain, with allodynia and hyperalgesia being the most common signs. Many patients with FM explore, express interest, and use complementary and alternative medicine to help manage symptoms and improve quality of life. However, little is known about the clinical recommendations provided by naturopathic doctors (NDs). Objective: To describe trends in assessment and treatment of patients with FM by NDs. Methods: Retrospectively, medical records of 200 patients with the FM ICD-10 code were reviewed from the Robert Schad Naturopathic Clinic. Of these records, 70 met inclusion criteria and were further analyzed. Comorbid conditions, health concerns, physical and psychological examinations, and treatment were recorded. Patients were excluded if informed consent for research was not signed. The project was approved by the Research Ethics Board of the Canadian College of Naturopathic Medicine. Results: Seventy patients met criteria and were included in the current analysis. Most patients identified as female (96%). Vitamin D (57%), magnesium (54%), omega-3 fish oil (53%), acupuncture by an acupuncturist (53%) or an ND (40%), B12 orally or by injection (40%), and probiotics (40%) were highly utilized treatments. A past/current medical history of digestive complaints (64%) and depression/mental illness (63%) were common comorbidities, alongside a history of arthritic conditions (53%) and anxiety (43%). A family history of arthritic conditions (47%) was also prevalent. The Widespread Pain Index and Symptom Severity tool (43%) was used to assess pain and other symptoms. No adverse effects of treatment were readily identifiable. Conclusion: Findings from this study reveal elements of both consistency and variability in the treatment recommendations from NDs in a teaching clinic environment. Future research that assesses or compares treatment recommendations for FM in other settings may be informative to better understand health services, the nature of individualized care, and patient experiences.
... This process of inflammation represents a physiological defense mechanism protecting the body from infection and diseases; however, it must be wellregulated in order to maintain homeostasis (inflammation vs. anti-inflammatory). Because n-6 PUFA content is much greater than n-3 PUFA in typical Western diets, controlling dietary AA allows a down-regulation of PG 2 synthesis and, consequently, anomalous inflammatory responses [32]. ...
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The beneficial effects of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) on human health are widely known. Humans are rather inefficient in synthesizing n-3 LC-PUFA; thus, these compounds should be supplemented in the diet. However, most Western human diets have unbalanced n-6/n-3 ratios resulting from eating habits and the fact that fish sources (rich in n-3 LC-PUFA) are not sufficient (worldwide deficit ~ 347,956 t/y) to meet the world requirements. In this context, it is necessary to find new and sustainable sources of n-3 LC-PUFA. Poultry products can provide humans n-3 LC-PUFA due to physiological characteristics and the wide consumption of meat and eggs. The present work aims to provide a general overview of the main strategies that should be adopted during rearing and postproduction to enrich and preserve n-3 LC-PUFA in poultry products. The strategies include dietary supplementation of α-Linolenic acid (ALA) or n-3 LC-PUFA, or enhancing n-3 LC-PUFA by improving the LA (Linoleic acid)/ALA ratio and antioxidant concentrations. Moreover, factors such as genotype, rearing system, transport, and cooking processes can impact the n-3 LC-PUFA in poultry products. The use of a multifactorial view in the entire production chain allows the relevant enrichment and preservation of n-3 LC-PUFA in poultry products.
... The ω-3 PUFAs derived from seafoods are known to contribute immune cell functions. The results have been shown that ω-3 PUFAs modulate both the innate and the adaptive immunity (Calder, 2017). The potent anti-inflammatory functions of ω-3 ...
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Aquafoods are diverse and rich in containing various health functional compounds which boost natural immunity. In this manuscript, the contents of biofunctional compounds such as vitamins, minerals, protein and amino acids, ω-3 polyunsaturated fatty acids, and pigments, etc. in various aquafoods like fishes, molluscs, crustaceans, seaweeds etc. are reported. The functional roles of those compounds are also depicted which enhance the immunecompetence and immunomodulation of the consumers. This paper provides an account of the recommended daily dietary intake level of those compounds for human. Those compounds available in aquafoods are recommended as they fight against various infectious diseases by enhancing immunity. Available reports on the bioactive compounds in aquafoods reveal the immunity boosting performances which may offer a new insight into controlling infectious diseases.
... Indeed, EPA and DHA are involved in all phases of life, from pre-and post-natal development to healthy aging, and in between through the maintenance of an effective immune system, neurological and cardiac functions. In addition, their consumption is linked to a lower risk of developing several pathologies such as neurodegenerative, cardiovascular and inflammatory diseases and cancers (Dyall and Michael-Titus, 2008;Riediger et al., 2009;Calder, 2017;Saini and Keum, 2018). ...
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The health benefits of a diet rich in omega-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA) no longer need to be proven. However, while health authorities attempt to increase the consumption of the n-3 LC-PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), data from the latest intake surveys demonstrate that EPA and DHA consumption is still too low. A push towards greater sustainability, and a rise in vegetarianism are pushing manufacturers to move from traditional fish oils towards alternative sources. Microalgae oils provide a source of n-3 LC-PUFA with a lower environmental impact and are produced using processes that limit damage to the oils. This review aims to report on oleaginous microalgae strains available for n-3 LC-PUFA production, the processes used for their growth and the extraction and refining processes for their oils. It also addresses the challenges inherent in these products and their fabrication, and some of the novel characteristics of microalgal oils, including their very high n-3 LC-PUFA content and the chemical structure of their triglycerides, that lead to exciting opportunities in their use as functional food ingredients.
... Fish oil, as the major source of omega-3 fatty acids, EPA and DHA, has been widely reported for its inflammatory mediation in cells, animal models and humans by curbing the production of the pro-inflammatory regulators, IL-6, IL-1β,TNF-α, IL-2, LTB4, PGE2, etc. [53,54]. EPA and DHA produce resolvins and DHA also gives rise to maresins and neuroprotectins through cyclooxygenase/LOX pathways [55]. Previous human studies based on healthy volunteers showed that increased intake of fish oil promoted the blood concentration of the anti-inflammatory resolvins, resolvin D 1 and D 2 [56]. ...
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Background Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Although fish oil has been used as an immunonutritional preparations for the treatment of sepsis patients, there is still controversy as to whether it is beneficial to them. We systematically reviewed published clinical trial data to evaluate the effectiveness of fish oil-containing nutrition supplementation in sepsis patients. Methods A systematic search was undertaken in PubMed, Embase, Chinese Biomedicine Database, the Cochrane Library and the China Knowledge Resource Integrated Database to obtain clinical controlled trails. RCTs on nutrition therapy containing fish oil among adult sepsis patients were selected for analysis in comparison with routine therapy. Results Twenty-five published trials were included in the meta-analysis. Fish oil-containing nutrition supplementation reduced the mortality compared with the control group (relative risk (RR) 0.74, I2 = 0%). Fish oil also shortened the ICU stay (MD −3.57 days; 95% CI −4.54, −2.59; p<0.00001; I2 = 76%), hospital stay (MD −9.92 days; 95% CI −15.37, −4.46; p = 0.0004; I2 = 91%) and the duration of mechanical ventilation support (MD −2.26; 95% CI −4.27, −0.26; p = 0.03; I2 = 83%). A subgroup analysis based on the route of administration revealed that parenteral administration of fish oil could reduce mortality in septic patients (RR =0.68, I2 = 0%), but no significant difference in mortality was observed in the fish oil group administered by enteral route (RR = 0.80, I2 = 0%). No statistically significant publication biases were detected for the above clinical endpoints (p>0.05). Conclusions Parenteral nutrition containing fish oil could significantly decrease mortality in sepsis patients while enteral administration could not. Fish oil-containing nutrition supplementation.
... For example, ω-3 PUFAs α linolenic acid can be converted into docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and prostaglandin (45). While biologically active derivatives of the ω-6 PUFAs arachidonic acid (AA) include PGs, thromboxane, hydroxyeicosatetraenoic acids and LTs (16,17,46,47). It is reported that dietary supplementation with EPA and DHA decreased low-density lipoprotein cholesterol (LDL-C) synthesis and increased bile acid synthesis and LDL-C clearance by LDL receptor, synergistically with estrogen (48). ...
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Probiotics have attracted much attention due to their ability to modulate host intestinal microbe, participate in nutrient metabolism or immunomodulatory. Both inflammatory bowel disease (IBD) and bowel cancer are digestive system disease, which have become a global public health problem due to their unclear etiology, difficult to cure, and repeated attacks. Disturbed gut microbiota and abnormal lipid metabolism would increase the risk of intestinal inflammation. However, the link between lipid metabolism, probiotics, and IBD is unclear. In this review, we found that different lipids and their derivatives have different effects on IBD and gut microbes. ω-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid, eicosapentaenoic acid, and their derivatives resolvin E1, resolvin D can inhibit oxidative stress and reactive oxygen species activate NFκB and MAPk pathway. While ω-6 PUFAs linoleic acid and arachidonic acid can be derived into leukotrienes and prostaglandins, which will aggravate IBD. Cholesterol can be converted into bile acids to promote lipid absorption and affect microbial survival and colonization. At the same time, it is affected by microbial bile salt hydrolase to regulate blood lipids. Low denstiy lipoprotein (LDL) is easily converted into oxidized LDL, thereby promoting inflammation, while high denstiy lipoprotein (HDL) has the opposite effect. Probiotics compete with intestinal microorganisms for nutrients or ecological sites and thus affect the structure of intestinal microbiota. Moreover, microbial short chain fatty acids, bile salt hydrolase, superoxide dismutase, glutathione, etc. can affect lipid metabolism and IBD. In conclusion, probiotics are directly or indirectly involved in lipids metabolism and their impact on IBD, which provides the possibility to explore the role of probiotics in improving gut health.
... EPA and DHA are valuable nutrients for human health since, for example, they play a crucial role in the prevention of several Non Communicable Diseases (NCDs) such as coronary heart disease and atherosclerosis (Kris-Etherton et al., 2002;Mozaffarian & Wu, 2011;Raatz et al., 2013) and are involved in the development of membrane structures, brain and retina, and in the regulation of metabolic and physiological function such as the reduction of blood triacylglycerols (Leslie et al., 2015) and the control of blood pressure (Miller et al., 2014). Moreover, the anti-oxidant and anti-inflammatory activities of EPA and DHA play a preventive effect against neurodegenerative and cancerogenic diseases (Calder, 2017;Sakai et al., 2017). ...
Article
Background Omega-3 fatty acids (FAs) are relevant commodities in the market since their important role in human wellbeing. As the worldwide demand is increasing, alternative sources and sustainable processes are needed to face the limited supply of the omega-3 FAs of fish origin. Microalgae provide a portfolio of biodiversity able to satisfy the quest for alternative sources and to match the need of sustainability for the production of these compounds. Scope and approach The review deepens the topic of sustainable production and supply by analyzing the current data available in scientific literature and providing a glance of the market of omega-3 FAs from different microalgal species. This was assessed in light of the technologies applicable to enhance and improve production. We analyzed and compared how traditional and innovative biotechnological approaches are exploited to maximize the ability of microalgae to produce omega-3 FAs, in particular eicosapentaenoic acid and docosahexaenoic acid (EPA and DHA). Key findings and conclusions This critical overview highlights that microalgal bioprospecting, combined with engineering approaches and with the study of the influence from the environment, can provide a reliable and sustainable alternative for omega-3 production. Unlocking the interdependence of these factors will play a key role for achieving the industrial scalability and standardization of the processes. Finally, the strategy to promote the consumer's acceptability of algae-based products will also be pivotal to substitute the current sources of omega-3 and therefore to address the sustainability challenges that Europe, as well as the rest of the world, is facing.
... The effects of certain nutrients on wound healing have been studied, e.g., arginine [4], glutamine [5], vitamin C [6], and fatty acids (FA) [7]. From all the above mentioned, polyunsaturated fatty acids (PUFA) n-3 modulate the production of pro-inflammatory cytokines (IL-1, IL-6, TNF-alfa) by their end products (such as leukotrienes, prostaglandins, and thromboxane) and thus exert dominant anti-inflammatory effects [8]. In contrast, the Nutrients 2022, 14, 2245 2 of 13 effect of n-6 PUFA is rather pro-inflammatory [9]. ...
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Polyunsaturated fatty acids (PUFA) play an important role in reparative processes. The ratio of PUFAs n-3 to n-6 may affect wound healing. The study aimed to evaluate the effect of dietary supplementation with n-3 and n-6 PUFA in two proportions on skin wounds in laboratory rats. Adult male Wistar rats received 20% fat emulsion with a ratio of 1.4:1 (group A) or 4.3:1 (group B) for n-3:n-6 PUFAs at a daily dose of 1 mL/kg. The control group received water under the same conditions. The animals were supplemented a week before and a week after the skin excision performed on the back. The level of wound closure, various parameters of oxidative stress, and plasma fatty acids composition were evaluated. Wound tissue samples were examined by electron microscopy. The administration of fat emulsions led to significant changes in plasma polyunsaturated fatty acid composition. The increased production of reactive nitrogen species, as well as more numerous newly formed blood vessels and a greater amount of highly organized collagen fibrils in both groups A and B may indicate more intensive healing of the skin wound in rats supplemented with polyunsaturated fatty acids in high n-3:n-6 ratio.
... Although airway mucosal immunity may play a crucial role in preventing progression to the more severe spectrum of COVID-19, easy-to-implement interventions to enhance airway mucosal immunity have not yet been identified. Growing evidence supports the hypothesis that both homeostasis of inflammation resolution and airway mucosal immunity may be largely mediated by a novel superfamily of autacoids, now termed specialized proresolving mediators (SPMs); the majority of SPMs are biosynthesized from the long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [5][6][7][8][9]. Importantly, a deficiency of EPA and DHA has been detected in populations throughout the world, and this issue is particularly severe in Western populations [10]. ...
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Background: Omega-3 fatty acids enhance immune response and modulate inflammation. This study aimed to determine the relationship between omega-3 fatty acid status and the severity of SARS-CoV-2 infection. Methods: Using a case-control design, we compared hospitalized patients with severe SARS-CoV-2 infection (cases, n = 73) with a group of ambulatory patients with mild SARS-CoV-2 infection (controls, n = 71). No patients were vaccinated against SARS-CoV-2. Results: The cases were older (p = 0.003), less educated (p = 0.001), had larger neck and smaller waist circumferences (p = 0.035 and p = 0.003, respectively), more frequently had diabetes (p < 0.001), consumed less fish (p < 0.001), consumed higher proportions of fried fish (p = 0.001), and had lower Omega-3 Index (O3I) values (p = 0.001) than controls. Cases had significantly lower rates of upper airway symptoms than controls. Lower O3I was associated with an increased likelihood of developing severe COVID-19 after adjusting for potential confounders (OR: 0.52; CI 0.32-0.86). Diabetes (OR: 4.41; CI 1.60-12.12), neck circumference (OR: 1.12; CI 1.03-1.21), and older age (OR: 1.03; CI 1.002-1.062) were also linked to COVID-19 severity. Fried fish consumption and low educational level were independent risk factors for severe COVID-19. Conclusions: This study suggests incorporating nutritional interventions to improve omega-3 status within nonpharmacological measures may help to reduce the severity of COVID-19.
... n-3 PUFA inhibit many aspects of inflammation (as leucocyte chemotaxis, adhesion molecule expression, leucocyte-endothelial interactions, production of prostaglandins and pro-inflammatory cytokines, and activation of the pro-inflammatory transcription factor nuclear factor κB). In addition, EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators, as resolvins [40,41]. Under typical western dietary conditions, human cells have a poor content of n-3 PUFA. ...
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Women show an increased risk of cognitive impairment and emotional disorders, such as anxiety and depression, when approaching menopause. Data on risk and protection factors have yielded robust evidence on the effects of lifestyle factors, such as diet, in preserving emotional and cognitive functioning. This review focused on the effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) on anxiety, depression, and cognition during the menopausal transition. This systematic review considered all articles published until 31 December 2021, and the search was performed on two databases, PubMed and Scopus. The fields of interest were “menopause”, “n-3 PUFA” and “emotional and cognitive aspects”. Out of the 361 articles found on PubMed and 283 on Scopus, 17 met inclusion criteria. They encompassed 11 human and 6 animal studies. Most studies reported relieved depressive symptoms in relation to n-3 PUFA intake. While controversial results were found on anxiety and cognition in humans, n-3 PUFA consistently reduced anxiety symptoms and improved cognition in animal studies. Taken together, n-3 PUFA intake shows beneficial effects on emotional and cognitive behaviours during menopause transition. However, further investigations could increase knowledge about the effectiveness of n-3 PUFA on psychological well-being in this delicate period of feminine life.
... ARA can be metabolized to prostaglandins (A2, E2, I2, and thromboxane A2) by cyclooxygenases-2 (COX-2), while leukotrienes (B4, C4, and E4) are biosynthesized from ARA by lipoxygenases (5-LOX) 41 . The influence of omega-3 and omega-6 fatty acids on the immune system has been widely surveyed 42 . PUFA show also a significant impact on the regulation of adipocyte differentiation and their function. ...
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An investigation of new ways to activate brown adipose tissue (BAT) is highly valuable, as it is a possible tool for obesity prevention and treatment. The aim of our study was to evaluate the relationships between dietary intake and BAT activity. The study group comprised 28 healthy non-smoking males aged 21–42 years. All volunteers underwent a physical examination and 75-g OGTT and completed 3-day food intake diaries to evaluate macronutrients and fatty acid intake. Body composition measurements were assessed using DXA scanning. An FDG-18 PET/MR was performed to visualize BAT activity. Brown adipose tissue was detected in 18 subjects (67% normal-weight individuals and 33% overweight/obese). The presence of BAT corresponded with a lower visceral adipose tissue (VAT) content (p = 0.04, after adjustment for age, daily kcal intake, and DXA Lean mass). We noted significantly lower omega-6 fatty acids (p = 0.03) and MUFA (p = 0.02) intake in subjects with detected BAT activity after adjustment for age, daily average kcal intake, and DXA Lean mass, whereas omega-3 fatty acids intake was comparable between the two groups. BAT presence was positively associated with the concentration of serum IL-6 (p = 0.01) during cold exposure. Our results show that BAT activity may be related to daily omega-6 fatty acids intake.
... Our results suggest that linseed supplementation (whatever the matrix) may limit AIEC-induced intestinal inflammation as shown by the lower fecal lipocalin-2 concentrations (a sensitive and non-invasive inflammation biomarker [46]) in the supplemented groups, without affecting the intestinal permeability. It is known that n-3 PUFAs have anti-inflammatory properties, particularly after stimuli that promote inflammation [48]. Indeed, after 12 weeks of supplementation, n-3 PUFAs should have been converted to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the active metabolic n-3 PUFA derivatives. ...
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The Western diet, rich in lipids and in n-6 polyunsaturated fatty acids (PUFAs), favors gut dysbiosis observed in Crohn's disease (CD). The aim of this study was to assess the effects of re-balancing the n-6/n-3 PUFA ratio in CEABAC10 transgenic mice that mimic CD. Mice in individual cages with running wheels were randomized in three diet groups for 12 weeks: high-fat diet (HFD), HFD + linseed oil (HFD-LS-O) and HFD + extruded linseed (HFD-LS-E). Then, they were orally challenged once with the Adherent-Invasive Escherichia coli (AIEC) LF82 pathobiont. After 12 weeks of diet, total energy intake, body composition, and intestinal permeability were not different between groups. After the AIEC-induced intestinal inflammation, fecal lipocalin-2 concentration was lower at day 6 in n-3 PUFAs supplementation groups (HFD-LS-O and HFD-LS-E) compared to HFD. Analysis of the mucosa-associated microbiota showed that the abundance of Prevotella, Para-prevotella, Ruminococcus, and Clostridiales was higher in the HFD-LS-E group. Butyrate levels were higher in the HFD-LS-E group and correlated with the Firmicutes/Proteobacteria ratio. This study demonstrates that extruded linseed supplementation had a beneficial health effect in a physically active mouse model of CD susceptibility. Additional studies are required to better decipher the matrix influence in the linseed supplementation effect. Citation: Plissonneau, C.; Sivignon, A.; Chassaing, B.; Capel, F.; Martin, V.; Etienne, M.; Wawrzyniak, I.; Chausse, P.; Dutheil, F.; Mairesse, G.; et al. Beneficial Effects of Linseed Supplementation on Gut Mucosa-Associated Microbiota in a Physically Active Mouse Model of Crohn's Disease. Int. J. Mol. Sci. 2022, 23, 5891. https://doi.org/10.3390/ ijms23115891 Academic Editors: Massimiliano Gasparrini and Luca Mazzoni
... DHA is an essential fatty acid that is ubiquitous in marine animals and plant plankton [9]. Previous studies have reported that the bioactivities of DHA, such as improvement in brain function [10], antitumor activity [11], regulation of lipid metabolism [12], regulation of glucose metabolism [13], antiinflammatory effect [14], and improvement on exercise training and performance [15]. Increasing evidence also supports the beneficial effects of DHA on skeletal muscle function, such as alleviating muscular atrophy [16], ameliorating endurance exercise capacity [17], and contributing in recovery from exhaustion [18]. ...
Article
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Background Obesity leads to a decline in the exercise capacity of skeletal muscle, thereby reducing mobility and promoting obesity-associated health risks. Dietary intervention has been shown to be an important measure to regulate skeletal muscle function, and previous studies have demonstrated the beneficial effects of docosahexaenoic acid (DHA; 22:6 ω-3) on skeletal muscle function. At the molecular level, DHA and its metabolites were shown to be extensively involved in regulating epigenetic modifications, including DNA methylation, histone modifications, and small non-coding microRNAs. However, whether and how epigenetic modification of mRNA such as N6-methyladenosine (m6A) mediates DHA regulation of skeletal muscle function remains unknown. Here, we analyze the regulatory effect of DHA on skeletal muscle function and explore the involvement of m ⁶ A mRNA modifications in mediating such regulation. Results DHA supplement prevented HFD-induced decline in exercise capacity and conversion of muscle fiber types from slow to fast in mice. DHA-treated myoblasts display increased mitochondrial biogenesis, while slow muscle fiber formation was promoted through DHA-induced expression of PGC1α. Further analysis of the associated molecular mechanism revealed that DHA enhanced expression of the fat mass and obesity-associated gene (FTO), leading to reduced m6A levels of DNA damage-induced transcript 4 ( Ddit4 ). Ddit4 mRNA with lower m6A marks could not be recognized and bound by the cytoplasmic m6A reader YTH domain family 2 (YTHDF2), thereby blocking the decay of Ddit4 mRNA. Accumulated Ddit4 mRNA levels accelerated its protein translation, and the consequential increased DDIT4 protein abundance promoted the expression of PGC1α, which finally elevated mitochondria biogenesis and slow muscle fiber formation. Conclusions DHA promotes mitochondrial biogenesis and skeletal muscle fiber remodeling via FTO/m ⁶ A/DDIT4/PGC1α signaling, protecting against obesity-induced decline in skeletal muscle function.
... In cells, the membrane FA composition influences the inflammatory response by affecting the production of inflammatory mediators [15]. In fact, the increase in the membrane content of n-3 PUFA (EPA and DHA), at the expense of the arachidonic acid (AA, 20:4n-6) content (an n-6 PUFA), is followed by an increase in the production of eicosanoids and resolvins [16]. Remarkably, it is well established that the inappropriate regulation of inflammation contributes to a range of human diseases. ...
Article
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In this review, the role of fatty acids (FA) in human pathological conditions, infertility in particular, was considered. FA and FA-derived metabolites modulate cell membrane composition, membrane lipid microdomains and cell signaling. Moreover, such molecules are involved in cell death, immunological responses and inflammatory processes. Human health and several pathological conditions are specifically associated with both dietary and cell membrane lipid profiles. The role of FA metabolism in human sperm and spermatogenesis has recently been investigated. Cumulative findings indicate F2 isoprostanes (oxygenated products from arachidonic acid metabolism) and resolvins (lipid mediators of resolution of inflammation) as promising biomarkers for the evaluation of semen and follicular fluid quality. Advanced knowledge in this field could lead to new scenarios in the treatment of infertility.
... The benefits of supplementation also manifest over varying time intervals for different diseases. In addition, the greatest benefits with omega-3 are believed to come from the daily intake of fatty fish (salmon, tuna, mackerel, herring and sardines) and from some seeds and vegetables [51]. However, none of the studies included here evaluated the current dietary habits of the participants, which could lead to significant bias. ...
Article
Aim: This systematic review examined the additional effect of taking omega-3 supplements on periodontal therapy. Methods: The focused question was "What is the possible effect of omega-3 supplementation concomitant to non-surgical periodontal therapy on clinical periodontal parameters?" Databases Cochrane, Embase, Google Scholar, PubMed, and Web of Science (January-July 2021) were searched to identify appropriate studies. Randomized clinical trials (RCT) about non-surgical therapy with omega-3 supplementation, with at least 3 months of supplementation period were included. Cochrane risk of bias tool version 2 and Grading of Recommendations Assessment, Development, and Evaluation were used. Results: A total of 1556 studies were found, of which eight studies met the inclusion criteria. All eight studies evaluated periodontal probing depth and clinical attachment loss; plaque and gingival inflammation were evaluated in seven studies. High variety of omega-3 dosage, different study lengths, questionable results from periodontal therapy (including test and control groups), high risk of bias and moderate quality of evidence prevented a satisfactory conclusion regarding the benefits of omega-3 supplementation. The studies' high heterogeneity avoided meta-analysis. Conclusion: Notwithstanding all limitations, the promising effects of omega-3 supplementation presented in two six-month studies encourage performing RCT with better-defined treatment protocols and greater methodological rigor.
Article
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease featuring progressive cognitive impairment. Although the etiology of late-onset AD remains unclear, the close association of AD with apolipoprotein E (APOE), a gene that mainly regulates lipid metabolism, has been firmly established and may shed light on the exploration of AD pathogenesis and therapy. However, various confounding factors interfere with the APOE -related AD risk, raising questions about our comprehension of the clinical findings concerning APOE . In this review, we summarize the most debated factors interacting with the APOE genotype and AD pathogenesis, depict the extent to which these factors relate to APOE -dependent AD risk, and discuss the possible underlying mechanisms.
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Excessive LDL cholesterol concentration together with subclinical inflammation, in which macrophages play a central role, are linked pathologies. The process starts with the accumulation of macrophages in white adipose tissue and the switch of their polarization toward a pro-inflammatory phenotype. The proportion of pro-inflammatory macrophages in adipose tissue is related to the main risk predictors of cardiovascular disease. The cholesterol content of phospholipids of cell membranes seems to possess a crucial role in the regulation of membrane signal transduction and macrophage polarization. Also, different fatty acids of membrane phospholipids influence phenotypes of adipose tissue macrophages with saturated fatty acids stimulating pro-inflammatory whereas ω3 fatty acids anti-inflammatory changes. The inflammatory status of white adipose tissue, therefore, reflects not only adipose tissue volume but also adipose tissue macrophages feature. The beneficial dietary change leading to an atherogenic lipoprotein decrease may therefore synergically reduce adipose tissue driven inflammation.
Article
Purpose: To develop an accelerated MRI method to quantify the epicardial adipose tissue (EAT) fatty acid composition (FAC) and test the hypothesis that eplerenone (EPL) shifts the EAT FAC toward unsaturation in obese mice. Methods: Undersampled multi-echo gradient echo imaging employing a dictionary-based compressed-sensing reconstruction and iterative decomposition with echo asymmetry and least-squares-based mapping (IDEAL) was developed, validated, and used to study EAT in obese mice scanned at 7T. Fully sampled and rate 2, 2.5, 3, and 3.5 undersampled image data were acquired, reconstructed, and assessed using RMSE and structural similarity (SSIM). Two groups of mice were studied: untreated (control, n = 10) and EPL-treated (n = 10) mice fed a high-fat high-sucrose diet. MRI included imaging of EAT FAC, EAT volume, and myocardial perfusion reserve. Results: Rate 3 acceleration provided RMSE <5% and structural similarity >0.85 for FAC MRI. After 6 weeks of diet, EPL-treated compared to untreated mice had a reduced EAT saturated fatty acid fraction (0.27 ± 0.09 vs. 0.39 ± 0.07, P < 0.05) and increased EAT unsaturation degree (4.37 ± 0.32 vs. 3.69 ± 0.58, P < 0.05). Also, EAT volume in EPL-treated compared to untreated mice was reduced (8.1 ± 0.6 mg vs. 11.4 ± 0.7 mg, P < 0.01), and myocardial perfusion reserve was improved (1.83 ± 0.15 vs. 1.61 ± 0.17, P < 0.05). Conclusion: Rate 3 accelerated FAC MRI enabled accurate quantification of EAT FAC in mice. EPL treatment shifted the EAT FAC toward increased unsaturation and was associated with improvement of coronary microvascular function.
Article
Воспаление – это состояние, которое сопутствует ряду заболеваний человека. Оно затрагивает множество типов клеток, химических медиаторов и взаимодействий. ЭПК и ДГК являются основными ω-3 ПНЖК, содержащимися в жирной рыбе и рыбьем жире. Есть клинические исследования, которые показывают, что эти ЖК способны частично ингибировать ряд аспектов воспаления. В статье приведен анализ литературных источников относительно вопросов патогенетических механизмов воспалительного и аутоиммунного процессов, системного воспаления, механизм действия ω-3 жирных кислот в воспалительной системе и принципы использования этих жирных кислот для лечения заболеваний с воспалительным компонентом. Дозозависимый эффект ω-3 ПНЖК на воспалительные реакции недостаточно хорошо описан в литературных источниках, но очевидно, что для достижения противовоспалительного эффекта необходима доза не менее 2 г в день. Механизм противовоспалительного действия ω-3 ПНЖК (ЭПК и ДГК) заключается в их влиянии на метаболизм арахидоновой кислоты. Следует заметить, что оптимального баланса ЖК в организме человека, даже при увеличении в рационе ω-3, невозможно достичь без уменьшения потребления жиров с содержанием ω-6 ЖК. Inflammation is a condition that accompanies a number of human diseases. It includes many types of cells, chemical mediators and interactions. EPA and DHA are the main 3 PUFAs found in oily fish and fish oil. There are clinical studies that show that these FAs are able to partially inhibit a number of aspects of inflammation. In the article, there are discussed the issues of pathogenetic mechanisms of inflammatory and autoimmune processes, systemic inflammation, the mechanism of action of ω-3 fatty acids in the inflammatory system, and the principles of using these fatty acids for treatment of diseases with inflammatory component. The dose-dependent effect of ω-3 PUFAson inflammatory reactions is not well described in the literature, but it is obvious that the dose of at least 2 g per day is needed to achieve anti-inflammatory effect. The mechanism of anti-inflammatory action of ω-3 PUFAs (EPA and DНА) is their effect on the metabolism of arachidonic acid. It should be noted that the optimal balance of fatty acids in the human body, even with the increase of ω-3 in the diet, cannot be achieved without reducing the consumption of fats with the content of ω-6 FA.
Article
Red blood cell (RBC) fatty acid (FA) patterns are becoming recognized as long-term biomarkers of tissue FA composition, but different analytical methods have complicated inter-study and international comparisons. Here we report RBC FA data, with a focus on the Omega-3 Index (EPA + DHA in % of total FAs in RBC), from samples of seven countries (USA, Canada, Italy, Spain, Germany, South Korea, and Japan) including 167,347 individuals (93% of all samples were from the US). FA data were generated by a uniform methodology from a variety of interventional and observational studies and from clinical laboratories. The cohorts differed in size, demographics, health status, and year of collection. Only the Canadian cohort was a formal, representative population-based survey. The mean Omega-3 Index of each country was categorized as desirable (>8%), moderate (>6% to 8%), low (>4% to 6%), or very low (≤4%). Only cohorts from Alaska (treated separately from the US), South Korea and Japan showed a desirable Omega-3 Index. The Spanish cohort had a moderate Omega-3 Index, while cohorts from the US, Canada, Italy, and Germany were all classified as low. This study is limited by the use of cohorts of convenience and small sample sizes in some countries. Countries undertaking national health status studies should utilize a uniform method to measure omega-3 FA levels.
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It is known that in the first year of life, the most intensive growth, maturation of the digestive tract and intestinal microbiota, the development of the child’s immune and nervous systems occur. A lot of evidence has been accumulated that the optimal composition of mother’s milk regulates the metabolism of the child and contributes to the prevention of diseases of various origins. One of the key components of breast milk that have a positive effect on the growth and development of the child are polyunsaturated fatty acids (PUFAs). Considering the prevalence of омега‑3 PUFA deficiency in the population, the most appropriate is the use of омега‑3 PUFAs (EPA + DHA) as part of IUD before pregnancy, throughout the entire period of gestation and breastfeeding.
Article
Background Breast cancer survivors (BCS) are at risk for psychoneurological symptoms (PNS) and inflammation for years following cancer treatment. Fish, particularly salmon, provides a rich source of omega-3 long chain fatty acids (omega-3LC), which has an anti-inflammatory effect. However, the benefit of omega-3LC on PNS is not well-known. Aims This study evaluated the feasibility and the initial efficacy of a personalized meal plan with dietary omega-3LC in reducing PNS. Methods A prospective, randomized controlled trial design (n = 46) was used to evaluate the feasibility of a personalized meal plan using two omega-3LC dose levels (high and low omega-3LC) in reducing PNS including pain, depression, fatigue, sleep, and stress. Results The recruitment rate was 4.9% with overall retention rate of 74% and 67.1% adherence to personalized meal plan and dietary procedures. Of participants who completed the investigation, 94% completed fish adherence logs and consumed ≥70% of the assigned quantity of fish. Saliva collection was 97.8% at baseline and 100% at follow-up. BCS in the high omega-3LC group had a significant decrease in pain (p < .01), perceived stress (p < .05), sleep (p < .001), depression (p < .001), and fatigue (p < .01) over the course of intervention. There were trends of PNS improvement in the low omega-3LC group but the differences did not reach statistical significance. Conclusion Our results support the feasibility of our investigational design, procedures, and intervention. The outcomes provide preliminary support for an expanded research effort using fish as a source of omega-3LC and personalized dietary planning as a vehicle for symptom self-management in BCS.
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Somatic symptom disturbance is among the strongest predictors of painful temporomandibular disorder (TMD). Related psychological constructs, such as anxiety and depression, respond therapeutically to omega-3 polyunsaturated fatty acids (PUFAs) in clinical trials. This cross-sectional study investigated associations between the omega-6/omega-3 PUFA ratio and somatic symptom disturbance and depressive symptoms in a community-based sample of 501 adults and determined whether these associations differed between adults with and without TMD or irritable bowel syndrome (IBS). Liquid chromatography tandem mass spectrometry quantified PUFAs in circulating erythrocytes. Somatic symptoms and depression were quantified using Symptom Checklist-90-Revised subscales. Presence or absence of TMD and IBS, respectively, were determined by clinical examination and Rome III screening questions. The standardized beta coefficient for the omega-6/omega-3 long-chain PUFA ratio was 0.26 (95% confidence limits (CL): 0.08, 0.43) in a multivariable linear regression model in which somatic symptom disturbance was the dependent variable. When modelling depressive symptoms as the dependent variable, the standardized beta coefficient was 0.17 (95% CL:0.01, 0.34). Both associations were stronger among TMD cases and IBS cases than among non-cases. Future randomized control trials that lower the omega-6/omega-3 PUFA ratio could consider somatic or depressive symptoms as a therapeutic target for TMD or IBS pain. Perspective : In people with painful TMD or IBS, a high ratio of n-6/n-3 PUFA was positively associated with somatic symptom disturbance and depressive symptoms. Both measures of psychological distress were elevated in people with painful TMD and IBS. Future randomized clinical trials will determine whether lowering the n-6/n-3 ratio is therapeutic for pain.
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The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular fatty acids (FA) and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labelled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome, and induced repartitioning of n-3 and n-6 polyunsaturated FAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics.
Chapter
Breast cancer is the most commonly diagnosed cancer worldwide and the second leading cause of cancer death in women. There is growing evidence showing that a healthy diet has a protective effect on breast cancer. However, the effect of dietary lipids on breast cancer is not clearly understood. Thus, we reviewed the association between dietary lipids and breast cancer in this chapter. It is well established that total dietary fat amount, fatty acid type, and timing of fat exposure can all determine their effect on breast cancer development, in terms of incidence, treatment, recurrence, and prognosis. Most epidemiological studies have shown that both high-fat diet and n-3 polyunsaturated fatty acid (PUFA)-deficient diet have an inverse effect on breast cancer development. The potential mechanisms associated with the anticancer effect of n-3 PUFA mainly involve suppressing biosynthesis of proinflammatory eicosanoid, influencing signaling transcriptional pathway to balance the proliferation and apoptosis, and regulating epigenetics and gut microbiota. Based on these findings, breast cancer patients or women with high breast cancer risk should be encouraged to improve their dietary fat habits, in order to reduce the cancer risk and to improve quality of life and long-term survival.
Chapter
Essential fatty acids such as omega-3 polyunsaturated fatty acids (n-3 PUFAs) and omega-6 (n-6) PUFAs are essential for the development and function of the brain. There are three potential mechanisms that link n-3 PUFAs and mental health: (1) Inflammation & Oxidative Stress (2) Microbiota & Immune System (3) Nervous System. In addition, n-3 PUFAs have been used as a treatment for several common psychiatric disorders, including depression, anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and dementia. This chapter provides a brief overview of the most updated basic and clinical research findings of n-3 PUFAs in psychiatric disorders. Last but not least, clinical guidelines and the level of evidence of n-3 PUFAs in psychiatric disorders will also be featured in the chapter.
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Air pollution, especially PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 μm) in China, is severe and related to a variety of diseases while the potential mechanisms have not been clearly clarified yet. This study was conducted using a randomized crossover trial protocol among young and healthy college students. Plasma samples were collected before, during, and post two typical air pollution waves with a washout interval of at least 2 weeks under true and sham air purification treatments, respectively. A total of 144 blood samples from 24 participants were included in the final analysis. Metabolomics analysis for the plasma samples was achieved by Ultrahigh Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS). Orthogonal Partial Least Squares Discrimination Analysis (OPLS-DA) and linear mixed-effect models were used to identify the differentially expressed metabolites and their associations with PM2.5 exposure. Further use MetaboAnalyst 5.0 to conduct pathway enrichment analysis and correlation analysis of differential metabolites. A total of 40 metabolites were identified to be differentially expressed between the true and sham air purification treatments, and eleven metabolites showed consistent significant changes upon outdoor, indoor, and time-weighted personal PM2.5 exposures. Short-term exposure to PM2.5 might cause disturbances in metabolic pathways such as linoleic acid metabolism, arachidonic acid metabolism, and tryptophan metabolism.
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Unsaturated fatty acids (UFAs) are fatty acids with one or more carbon-carbon double bonds (C=C). They are building blocks of structurally complex lipids. According to the position of C=C bond in the UFAs, there are multiple isomers with different physiological activities. Therefore, an accurate understanding of UFAs is essential. Combining Paternò-Büchi (PB) reaction with tandem mass spectrometry (MS/MS) analysis has been successfully used to identify unsaturated lipids in bio-samples. However, there are still some challenges, such as low reactive rate and low MS response of PB products. In this study, 3-pyridinecarboxaldehyde (3-PYA) was selected as an efficient PB reagent for the first time. According to the nitrogen rule, introduction of nitrogen did not only make the target MS and MS/MS ions to be easily identified but also increase the ionization efficiency significantly. The developed method in this study demonstrated greater efficiency and sensitivity for the identification of UFAs in total lipid extracts from bovine liver compared with other commonly used PB reagents.
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Food supplements based on fermented Carica papaya and Morinda citrifolia, known for their immune modulating, redox balancing, and anti-inflammatory effects, were added to conventional treatment protocols prescribed to patients recovering after severe and moderate COVID-19 disease in order to alleviate long-lasting post-COVID symptoms. A randomized single-center placebo-controlled clinical laboratory study was designed and performed (total number of participants 188, with delta variant of virus 157, with omicron 31). Clinical statuses were assessed using computer tomography, electrocardiography, a questionnaire, and physical endurance. Plasma cytokines (IL-6, IL-8, IL-17A, and INF-gamma), nitrate/nitrite ratio, antioxidant activity (AOA), and polymorphonuclear leukocyte (PMN) ATP levels were determined before and 20 days following the addition of 28 g of fermented supplements twice per day. The capacity of PMN to phagocyte and the oral-nasal-pharyngeal microbiota were assessed. Clinical symptoms, IL-6, IL-8, and nitric oxide metabolites diminished significantly compared to the placebo group and their background expression. The PMN capacity to phagocyte, AOA, and ATP content remarkably increased. The oral-nasal-pharyngeal microbiota were unchanged. On these grounds, we suggest that fermented tropical fruits could efficiently diminish post-COVID clinical symptoms through several immune-modulating, redox balancing, and pro-energy mechanisms.
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Acute variceal bleeding, a crucial complication of liver cirrhosis requires high energy expenditures but gastrointestinal bleeding limits enteral feeding in the acute stage. We investigated the safety and efficacy of ω-3 fatty acid-enriched parenteral nutrition in acute variceal bleeding patients. In this retrospective study, a total of 208 cirrhotic patients with acute variceal bleeding who underwent parenteral nutrition in the absence of enteral nutrition were enrolled. Among the patients, 86 patients received ω-3 fatty-acid-enriched parenteral nutrition. The primary endpoint was to evaluate the duration of hospital stay and the presence of clinical complications of liver cirrhosis. The mean age of the patients enrolled was 54.9 years-old and 185 patients (88.9%) were male. The cause of liver cirrhosis, Child-Pugh score and comorbidities were statistically not different. Patients with ω-3 enriched parenteral nutrition had a significantly lower systolic blood pressure and total bilirubin levels. The difference in the in-hospital mortality (P = .813) or rate of complications (P = .880) was not statistically significant. The duration of hospital stay was significantly shorter in the patients who underwent ω-3 fatty acid-enriched parenteral nutrition (10.7 ± 7.3 vs 7.9 ± 4.2 days, P = .001). In liver cirrhosis patients with acute variceal bleeding, ω-3 fatty acid-enriched parenteral nutrition significantly decreased the length of hospital stay. Further prospective studies to consolidate these findings are warranted.
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Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0-4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify important FA changes for plasma phosphatidylcholine (PC), cholesteryl ester (CE) and triglyceride (TAG) and for blood mononuclear cells (MNC), red blood cells (RBC) and platelets (PLAT). Dose-dependent increases in EPA + DHA were matched by decreases in several n-6 polyunsaturated fatty acids (PUFA) in PC, CE, RBC and PLAT, but were predominantly compensated for by oleic acid in TAG. Changes were observed for all FA classes in MNC. Consequently the n-6:n-3 PUFA ratio was reduced in a dose-dependent manner in all pools after 12 months (37%-64% of placebo in the four portions group). We conclude that the profile of the FA decreased in exchange for the increase in EPA + DHA following supplementation differs by FA pool with implications for understanding the impact of n-3 PUFA on blood lipid and blood cell biology.
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The high incidence of cardiovascular disease (CVD) in chronic kidney disease (CKD) is related partially to chronic inflammation. n-3 Fatty acids have been shown to have anti-inflammatory effects and to reduce the risk of CVD. Specialized Proresolving Lipid Mediators (SPMs) derived from the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) actively promote the resolution of inflammation. This study evaluates the effects of n-3 fatty acid supplementation on plasma SPMs in patients with CKD. In a double-blind, placebo-controlled intervention of factorial design, 85 patients were randomized to either n-3 fatty acids (4 g), Coenzyme Q10 (CoQ) (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. The SPMs 18-HEPE, 17-HDHA, RvD1, 17R-RvD1, and RvD2, were measured in plasma by liquid chromatography-tandem mass spectrometry before and after intervention. Seventy four patients completed the 8 weeks intervention. n-3 Fatty acids but not CoQ significantly increased (P < 0.0001) plasma levels of 18-HEPE and 17-HDHA, the upstream precursors to the E- and D-series resolvins, respectively. RvD1 was significantly increased (P = 0.036) after n-3 fatty acids, but no change was seen in other SPMs. In regression analysis the increase in 18-HEPE and 17-HDHA after n-3 fatty acids was significantly predicted by the change in platelet EPA and DHA, respectively. SPMs are increased after 8 weeks n-3 fatty acid supplementation in patients with CKD. This may have important implications for limiting ongoing low grade inflammation in CKD. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
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Intravenous fish oil (FO) lipid emulsions (LEs) are rich in ω-3 polyunsaturated fatty acids, which exhibit anti-inflammatory and immunomodulatory effects. We previously demonstrated that FO containing emulsions may be able to decrease mortality and ventilation days in the critically ill. Over the last year, several additional randomized controlled trials (RCTs) of FO containing emulsions have been published. Therefore, the purpose of this systematic review was to update our systematic review aimed to elucidate the efficacy of FO-containing emulsions on clinical outcomes in the critically ill. We searched computerized databases from 1980 to 2014. We included 4 new RCTs conducted in critically ill adult patients that evaluated FO containing emulsions in parenterally or enterally fed patients. A total of 10 RCTs (n = 733) met inclusion criteria. The mean methodological score was 8 (range, 3-12). No effect on overall mortality was found. When the results of 5 RCTs that reported infections were aggregated, FO containing emulsions significantly reduced infections (RR 0.64; 95% CI, 0.44-0.92; P = 0.02, heterogeneity I (2) = 0%). Subgroup analysis demonstrated that predominantly enteral nutrition (EN) based trials showed a tendency towards a reduction in mortality (RR 0.69; 95% CI, 0.40-1.18, P = 0.18, heterogeneity I (2) = 35%). High quality trials showed a significant reduction in hospital length of stay (LOS) (WMD -7.42; 95% CI, -11.89, -2.94, P = 0.001) although low quality trials had no effect (P = 0.45); test for subgroup differences on hospital LOS was significant (P = 0.001). FO containing emulsions may be associated with a reduction in infections, as well as could be associated with a reduction in duration of ventilation and hospital length of stay. Further large scale RCTs, which should aim to consolidate potential positive treatment effects, are warranted.
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The effect of a flaxseed oil-based diet on tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) synthesis was examined in healthy volunteers. Use of flaxseed oil in domestic food preparation for 4 wk inhibited TNF alpha and IL-1 beta production by approximately 30%. Fish-oil supplementation (9 g/d) continued for a further 4 wk; TNF alpha and IL-1 beta synthesis were inhibited by 74% and 80%, respectively. There was a significant inverse exponential relation between TNF alpha or IL-1 beta synthesis and mononuclear cell content of eicosapentaenoic acid (EPA), an n--3 fatty acid derived from ingested EPA (fish oil) or metabolism of ingested alpha-linolenic acid (flaxseed oil). Cytokine production decreased as cellular EPA increased to approximately 1% of total fatty acids. Further increases in EPA content did not result in further decreases in cytokine production. The results indicate that vegetable oils rich in n--3 fatty acids inhibit TNF alpha and IL-1 beta synthesis.
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The intake of ω-3 polyunsaturated fatty acids (PUFAs), which are abundant in marine fish meat and oil, has been shown to exert many beneficial effects. The mechanisms behind those effects are numerous, including interference with the arachidonic acid cascade that produces pro-inflammatory eicosanoids, formation of novel bioactive lipid mediators, and change in the pattern of secreted adipocytokines. In our study, we show that eicosapentaenoic acid (EPA) increases secreted adiponectin from 3T3-L1 adipocytes and in plasma of mice as early as 4 days after initiation of an EPA-rich diet. Using 3T3-L1 adipocytes, we report for the first time that 15-deoxy-δ(12,14)-PGJ3 (15d-PGJ3), a product of EPA, also increases the secretion of adiponectin. We demonstrate that the increased adiponectin secretion induced by 15d-PGJ3 is partially peroxisome proliferator-activated receptor-gamma (PPAR-γ)-mediated. Finally, we show that 3T3-L1 adipocytes can synthesize 15d-PGJ3 from EPA. 15d-PGJ3 was also detected in adipose tissue from EPA-fed mice. Thus, these studies provide a novel mechanism(s) for the therapeutic benefits of ω-3 polyunsaturated fatty acids dietary supplementation.
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Peroxisome proliferator-activated receptors (PPARs) α and γ are key regulators of lipid homeostasis and are activated by a structurally diverse group of compounds including fatty acids, eicosanoids, and hypolipidemic drugs such as fibrates and thiazolidinediones. While thiazolidinediones and 15-deoxy-Δ12,14-prostaglandin J2 have been shown to bind to PPARγ, it has remained unclear whether other activators mediate their effects through direct interactions with the PPARs or via indirect mechanisms. Here, we describe a novel fibrate, designated GW2331, that is a high-affinity ligand for both PPARα and PPARγ. Using GW2331 as a radioligand in competition binding assays, we show that certain mono- and polyunsaturated fatty acids bind directly to PPARα and PPARγ at physiological concentrations, and that the eicosanoids 8(S)-hydroxyeicosatetraenoic acid and 15-deoxy-Δ12,14-prostaglandin J2 can function as subtype-selective ligands for PPARα and PPARγ, respectively. These data provide evidence that PPARs serve as physiological sensors of lipid levels and suggest a molecular mechanism whereby dietary fatty acids can modulate lipid homeostasis.
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Estimation of the intake of oily fish at a population level is difficult. The measurement of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in biological samples may provide a useful biomarker of intake. We identified the most appropriate biomarkers for the assessment of habitual oily fish intake and changes in intake by elucidating the dose- and time-dependent response of EPA and DHA incorporation into various biological samples that represent roles in fatty acid transport, function, and storage. This was a double-blind, randomized, controlled intervention trial in 204 men and women that lasted 12 mo. EPA and DHA capsules were provided in a manner to reflect sporadic consumption of oily fish (ie, 1, 2, or 4 times/wk). EPA and DHA were assessed at 9 time points over 12 mo in 9 sample types (red blood cells, mononuclear cells, platelets, buccal cells, adipose tissue, plasma phosphatidylcholine, triglycerides, cholesteryl esters, and nonesterified fatty acids). A dose response (P < 0.05) was observed for EPA and DHA in all pools except for red blood cell EPA (P = 0.057). EPA and DHA measures in plasma phosphatidylcholine and platelets were best for the discrimination between different intakes (P < 0.0001). The rate of incorporation varied between sample types, with the time to maximal incorporation ranging from days (plasma phosphatidylcholine) to months (mononuclear cells) to >12 mo (adipose tissue). Plasma phosphatidylcholine EPA plus DHA was identified as the most suitable biomarker of acute changes in EPA and DHA intake, and platelet and mononuclear cell EPA plus DHA were the most suitable biomarkers of habitual intake. This trial was registered at Current Controlled Trials (www.controlled-trials.com) as ISRCTN48398526.
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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and bones. The n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (ARA) is the precursor of inflammatory eicosanoids which are involved in RA. Some therapies used in RA target ARA metabolism. Marine n-3 PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) found in oily fish and fish oils decrease the ARA content of cells involved in immune responses and decrease the production of inflammatory eicosanoids from ARA. EPA gives rise to eicosanoid mediators that are less inflammatory than those produced from ARA and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving, although little is known about these latter mediators in RA. Marine n-3 PUFAs can affect other aspects of immunity and inflammation relevant to RA, including dendritic cell and T cell function and production of inflammatory cytokines and reactive oxygen species, although findings for these outcomes are not consistent. Fish oil has been shown to slow the development of arthritis in animal models and to reduce disease severity. A number of randomised controlled trials of marine n-3 PUFAs have been performed in patients with RA. A systematic review included 23 studies. Evidence is seen for a fairly consistent, but modest, benefit of marine n-3 PUFAs on joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity, and use of non-steroidal anti-inflammatory drugs.
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Asthma is a disease of airway inflammation that in most cases fails to resolve. The resolution of inflammation is an active process governed by specific chemical mediators, including D-series resolvins. In this study, we determined the impact of resolvin D1 (RvD1) and aspirin-triggered RvD1 (AT-RvD1) on the development of allergic airway responses and their resolution. Mice were allergen sensitized, and RvD1, AT-RvD1 (1, 10, or 100 ng), or vehicle was administered at select intervals before or after aerosol allergen challenge. RvD1 markedly decreased airway eosinophilia and mucus metaplasia, in part by decreasing IL-5 and IκBα degradation. For the resolution of established allergic airway responses, AT-RvD1 was even more efficacious than RvD1, leading to a marked decrease in the resolution interval for lung eosinophilia, decrements in select inflammatory peptide and lipid mediators, and more rapid resolution of airway hyperreactivity to methacholine. Relative to RvD1, AT-RvD1 resisted metabolic inactivation by macrophages, and AT-RvD1 significantly enhanced macrophage phagocytosis of IgG-OVA-coated beads in vitro and in vivo, a new proresolving mechanism for the clearance of allergen from the airways. In conclusion, RvD1 and AT-RvD1 can serve as important modulators of allergic airway responses by decreasing eosinophils and proinflammatory mediators and promoting macrophage clearance of allergen. Together, these findings identify D-series resolvins as potential proresolving therapeutic agents for allergic responses.
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There is accumulating evidence that omega-3 fatty acids may modulate immune responses. When monocytes were differentiated to dendritic cells (DCs) in the presence of docosahexaenoic acid (DHA), the expression of costimulatory and antigen presentation markers was altered in a concentration-dependent way, positively or negatively, depending on the markers tested and the maturation stage of the DCs. Changes induced by eicosapentaenoic acid and linoleic acid were similar but less intense than those of DHA, whereas oleic acid had almost no effect. DHA-treated, mature DCs showed inhibition of IL-6 expression and IL-10 and IL-12 secretion, and their lymphoproliferative stimulation capacity was impaired. The phenotypic alterations of DCs induced by DHA were similar to those already reported for Rosiglitazone (Rosi), a peroxisome proliferator-activated receptor gamma (PPAR gamma) activator, and the retinoid 9-cis-retinoic acid (9cRA), a retinoid X receptor (RXR) activator. Moreover, DHA induced the expression of PPAR gamma target genes pyruvate dehydrogenase kinase-4 and aP-2 in immature DCs. The combination of DHA with Rosi or 9cRA produced additive effects. Furthermore, when DCs were cultured in the presence of a specific PPAR gamma inhibitor, all of the changes induced by DHA were blocked. Together, these results strongly suggest that the PPAR gamma:RXR heterodimer is the pathway component activated by DHA to induce its immunomodulatory effect on DCs.
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Inflammation is a physiological response to tissue trauma or infection, but leukocytes, which are the effector cells of the inflammatory process, have powerful tissue remodelling capabilities. Thus, to ensure their precise localisation, passage of leukocytes from the blood into inflamed tissue is tightly regulated. Recruitment of blood borne neutrophils to the tissue stroma occurs during early inflammation. In this process, peptide agonists of the chemokine family are assumed to provide a chemotactic stimulus capable of supporting the migration of neutrophils across vascular endothelial cells, through the basement membrane of the vessel wall, and out into the tissue stroma. Here, we show that, although an initial chemokine stimulus is essential for the recruitment of flowing neutrophils by endothelial cells stimulated with the inflammatory cytokine tumour necrosis factor-alpha, transit of the endothelial monolayer is regulated by an additional and downstream stimulus. This signal is supplied by the metabolism of the omega-6-polyunsaturated fatty acid (n-6-PUFA), arachidonic acid, into the eicosanoid prostaglandin-D(2) (PGD(2)) by cyclooxygenase (COX) enzymes. This new step in the neutrophil recruitment process was revealed when the dietary n-3-PUFA, eicosapentaenoic acid (EPA), was utilised as an alternative substrate for COX enzymes, leading to the generation of PGD(3). This alternative series eicosanoid inhibited the migration of neutrophils across endothelial cells by antagonising the PGD(2) receptor. Here, we describe a new step in the neutrophil recruitment process that relies upon a lipid-mediated signal to regulate the migration of neutrophils across endothelial cells. PGD(2) signalling is subordinate to the chemokine-mediated activation of neutrophils, but without the sequential delivery of this signal, neutrophils fail to penetrate the endothelial cell monolayer. Importantly, the ability of the dietary n-3-PUFA, EPA, to inhibit this process not only revealed an unsuspected level of regulation in the migration of inflammatory leukocytes, it also contributes to our understanding of the interactions of this bioactive lipid with the inflammatory system. Moreover, it indicates the potential for novel therapeutics that target the inflammatory system with greater affinity and/or specificity than supplementing the diet with n-3-PUFAs.
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The relationship between fluctuating cytokine concentrations in plasma and the outcome of sepsis is complex. We postulated that early measurement of the activation of nuclear factor κB (NF-κB), a transcriptional regulatory protein involved in proinflammatory cytokine expression, may help to predict the outcome of sepsis. We determined NF-κB activation in peripheral blood mononuclear cells of 34 patients with severe sepsis (23 survivors and 11 nonsurvivors) and serial concentrations of inflammatory cytokines (interleukin-6, interleukin-1, and tumor necrosis factor) and various endogenous antagonists in plasma. NF-κB activity was significantly higher in nonsurvivors and correlated strongly with the severity of illness (APACHE II score), although neither was related to the cytokine levels. Apart from NF-κB activity, the interleukin-1 receptor antagonist was the only cytokine tested whose level in plasma was of value in predicting mortality by logistic regression analysis. These results underscore the prognostic value of early measurement of NF-κB activity in patients with severe sepsis.
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The study examined the ability of dietary n-3 fatty acids to modify mouse peritoneal macrophage glycerophospholipid molecular species and peptidoleukotriene synthesis. After a 2-week feeding period, fish versus corn oil feeding significantly (P less than 0.01) lowered n-6 polyunsaturated fatty acid (PUFA) mol % levels, i.e., arachidonic acid (20:4n-6) in diacylphosphatidylserine (PtdSer), diacylphosphatidylinositol (PtdIns), diacylglycerophosphoethanolamine (PtdEtn), alkenylacylglycerophosphoethanolamine (PlsEtn), and diacylglycerophosphocholine (PtdCho). A notable exception was alkylacylglycerophosphocholine (PakCho), where only moderate decreases in 16:0-20:4n-6 and 18:0-20:4n-6 species were observed after fish oil supplementation. The predominant n-3 PUFA in macrophage phospholipid subclasses was docosapentaenoic acid (22:5n-3). The major n-3 species were 18:0-22:5n-3 in PtdIns, PtdSer, glycerophosphoethanolamines (EtnGpl) and 16:0-22:5n-3 in PtdCho and PlsEtn. The major n-3-containing species in PakCho were 16:0-20:5n-3 and 18:1-22:6n-3. These findings indicate that n-3 PUFA are differentially incorporated into macrophage phospholipid subclasses after dietary fish oil supplementation, and suggest that phospholipid remodeling enzymes selectively discriminate between substrates based on compatibility of sn-1 covalent linkage and the composition of the sn-1 and sn-2 aliphatic chains. Macrophage peptidoleukotriene synthesis was also strongly influenced after fish oil feeding; the LTC5/LTC4 ratio was significantly higher (P less than 0.01) in fish oil-fed animals than in corn oil-fed animals, 0.85 versus 0.01, respectively. These ratios were subsequently compared to phospholipid molecular species 20:5n-3/20:4n-6 ratios in order to determine potential sources of eicosanoid precursors.
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Improvement in survival to endotoxin has been seen after pretreatment with cyclooxygenase inhibitors. Because eicosapentaenoic acid (EPA), found in menhaden oil, competitively inhibits cyclooxygenase, we fed two groups of guinea pigs diets, in which the fat source was either menhaden or safflower oil, for 6 wk. A third group was allowed the safflower oil diet ad libitum. Menhaden oil-fed animals showed enhanced survival compared with safflower oil control animals 20 h after endotoxin (87 vs 63%, p less than 0.05). Ad libitum-fed safflower oil animals survived least well, with 47% alive at 20 h (p less than 0.005 vs menhaden oil group). We conclude that feeding animals a diet whose predominant lipid source is fish oil significantly improves survival after endotoxin. Dietary fat should be viewed not only as a caloric source but as a pharmacologically active substance that can have profound effects on the host's response to toxic insults.
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A recently published study (1) provides new evidence that omega-3 fatty acids have a role in the primary prevention of coronary heart disease (CHD). This new publication included pooled data from 19 cohort studies conducted in 16 countries and including over 45,000 individuals with a median follow-up time of 10 years. Importantly, omega-3 fatty acid concentrations in blood or tissue compartments at study entry were used as the measure of exposure. It was found that each of the four omega-3 fatty acids reported α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) was associated with reduced risk of fatal CHD, with about a 10% reduction in relative risk (RR) for each one standard deviation increase in concentration of the omega-3 fatty acid. These findings make a very valuable contribution to the ongoing discussion about the role of omega-3 fatty acids in cardiovascular disease (CVD) and provide further evidence to support recommendations for the population to consume these fatty acids as part of a healthy diet.
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The n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may reduce low-grade inflammation associated with obesity. The relationship between therapeutic response to n-3 PUFAs and modification of the transcriptome in obesity or metabolic syndrome remains to be explored. Blood samples were obtained from women with obesity before and after three-months supplementation with a moderate dose of n-3 PUFAs (1.8 g EPA + DHA per day) or from controls. n-3 PUFAs (GC) and plasma concentrations of lipoxins, resolvins, protectin X (GC-MS/MS) and inflammatory markers (ELISA) were measured. Whole blood transcriptome was assayed using microarray. Women supplemented with n-3 PUFAs for 3 months had significantly higher levels of EPA and DHA in plasma phosphatidylcholine. n-3 PUFA supplementation, in contrast to placebo, significantly decreased the concentrations of several inflammatory markers (SELE, MCP-1, sVCAM-1, sPECAM-1, and hsCRP), fasting triglycerides and insulin and increased the concentrations of pro-resolving DHA derivatives in plasma. The microarray data demonstrated effects of n-3 PUFAs on PPAR-?, NRF2 and NF-?B target genes. N-3 PUFAs increased DHA-derived pro-resolving mediators in women with obesity. Elevated resolvins and up-regulation of the resolvin receptor occurred in parallel with activation of PPAR-? target genes related to lipid metabolism and of NRF2 up-regulated antioxidant enzymes.
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Alpha-linolenic acid (ALA) is an essential fatty acid and the substrate for the synthesis of longer-chain, more unsaturated ω-3 fatty acids, eicosapentaenoic acid (EPA), docosapentaenoic acid and docosahexaenoic acid (DHA). EPA and DHA are associated with human health benefits. The primary source of EPA and DHA is seafood. There is a need for sustainable sources of biologically active ω-3 fatty acids. Certain plants contain high concentrations of ALA and stearidonic acid (SDA). Here we review the literature on the metabolism of ALA and SDA in humans, the impact of increased ALA and SDA consumption on concentrations of EPA and DHA in blood and cell lipid pools, and the extent to which ALA and SDA might have health benefits. Although it is generally considered that humans have limited capacity for conversion of ALA to EPA and DHA, sex differences in conversion to DHA have been identified. If conversion of ALA to EPA and DHA is limited, then ALA may have a smaller health benefit than EPA and DHA. SDA is more readily converted to EPA and appears to offer better potential for health improvement than ALA. However, conversion of both ALA and SDA to DHA is limited in most humans.
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Recent years have seen the description and elucidation of a new class of anti-inflammatory and pro-resolving lipid mediators. The arachidonic acid (AA) -derived compounds in this class are called lipoxins and have been described in great detail since their discovery thirty years ago. The new players are mediators derived from fish oil omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), called resolvins, protectins and maresins. Taken together, these mediators are also called specialized pro-resolution mediators (SPMs). As compared to the AA/EPA/DHA-derived compounds, research regarding mediators formed from the n-3 and n-6 docosapentaenoic acids (DPAn-3 and DPAn-6) is sparse. However, mono- di- and trihydroxy derivates of the DPAs have anti-inflammatory properties as well, even though mechanisms of their anti-inflammatory action have not been fully elucidated. This review aims to summarize current knowledge regarding the DPA-derived SPMs and their actions.
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The purpose of this article is to describe the structure, function and metabolism of fatty acids and lipids that are of particular importance in the context of parenteral nutrition. Lipids are a heterogeneous group of molecules that share the common property of hydrophobicity. Lipids range in structure from simple short hydrocarbon chains to more complex molecules, including triacylglycerols, phospholipids and sterols and their esters. Lipids within each class may differ structurally. Fatty acids are common components of complex lipids, and these differ according to chain length and the presence, number and position of double bonds in the hydrocarbon chain. Structural variation among complex lipids and among fatty acids gives rise to functional differences that result in different impacts upon metabolism and upon cell and tissue responses. Fatty acids and complex lipids exhibit a variety of structural variations that influence their metabolism and their functional effects. © 2015 S. Karger AG, Basel.
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Inflammation is a condition which contributes to a range of human diseases. It involves a multitude of cell types, chemical mediators, and interactions. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 (n-3) fatty acids found in oily fish and fish oil supplements. These fatty acids are able to partly inhibit a number of aspects of inflammation including leukocyte chemotaxis, adhesion molecule expression and leukocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid, production of inflammatory cytokines, and T-helper 1 lymphocyte reactivity. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of marine n-3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B so reducing expression of infl