scholarly journals Omega-3 fatty acids and inflammatory processes: from molecules to man

2017 ◽  
Vol 45 (5) ◽  
pp. 1105-1115 ◽  
Author(s):  
Philip C. Calder

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.

2020 ◽  
Vol 79 (4) ◽  
pp. 404-416 ◽  
Author(s):  
Philip C. Calder

Inflammation is a normal part of the immune response and should be self-limiting. Excessive or unresolved inflammation is linked to tissue damage, pathology and ill health. Prostaglandins and leukotrienes produced from the n-6 fatty acid arachidonic acid are involved in inflammation. Fatty acids may also influence inflammatory processes through mechanisms not necessarily involving lipid mediators. The n-3 fatty acids EPA and DHA possess a range of anti-inflammatory actions. Increased content of EPA and DHA in the membranes of cells involved in inflammation has effects on the physical nature of the membranes and on the formation of signalling platforms called lipid rafts. EPA and DHA interfere with arachidonic acid metabolism which yields prostaglandins and leukotrienes involved in inflammation. EPA gives rise to weak (e.g. less inflammatory) analogues and both EPA and DHA are substrates for the synthesis of specialised pro-resolving mediators. Through their effects on early signalling events in membranes and on the profile of lipid mediators produced, EPA and DHA alter both intracellular and intercellular signals. Within cells, this leads to altered patterns of gene expression and of protein production. The net result is decreased production of inflammatory cytokines, chemokines, adhesion molecules, proteases and enzymes. The anti-inflammatory and inflammation-resolving effects of EPA and DHA are relevant to both prevention and treatment of human diseases that have an inflammatory component. This has been widely studied in rheumatoid arthritis where there is good evidence that high doses of EPA + DHA reduce pain and other symptoms.


1964 ◽  
Vol 42 (3) ◽  
pp. 365-376 ◽  
Author(s):  
R. L. Lyman ◽  
Angela Shannon ◽  
Rosemarie Ostwald ◽  
P. Miljanich

The effects of physiological doses of estradiol and testosterone on plasma cholesteryl ester and phospholipid fatty acid composition were investigated in castrated male rats. The animals were killed after 3 weeks on experiment, and their plasma cholesteryl esters and phospholipids were analyzed and compared with those of intact female and male rats.Estradiol appeared to be responsible for the increased proportion of plasma cholesteryl arachidonate seen in the female or estrogen-injected rats since the proportion of cholesteryl arachidonate in castrated control rats was lower and similar to that of male or testosterone-treated rats. Plasma phospholipids of female and estradiol-injected rats had a higher percentage of stearic acid relative to palmitic acid. On the other hand, male, castrated control and testosterone-treated rats had higher proportions of palmitic acid. Fractionation of the plasma phospholipids into cephalins, lecithins, sphingomyelins, and lysolecithins, and analyses of their fatty acids, revealed that a principal effect of estradiol was to increase proportions and amounts of stearic and arachidonic acids in the lecithin fraction.The results suggest that estradiol may influence the synthesis of a lecithin rich in stearic and arachidonic acid. A possible relationship between the arachidonic-acid-rich lecithin and the higher percentage of cholesteryl arachidonate in estradiol-treated rats is discussed.


2001 ◽  
Vol 90 (2) ◽  
pp. 670-677 ◽  
Author(s):  
Jørn W. Helge ◽  
Ben J. Wu ◽  
Mette Willer ◽  
Jens R. Daugaard ◽  
Leonard H. Storlien ◽  
...  

Training improves insulin sensitivity, which in turn may affect performance by modulation of fuel availability. Insulin action, in turn, has been linked to specific patterns of muscle structural lipids in skeletal muscle. This study investigated whether regular exercise training exerts an effect on the muscle membrane phospholipid fatty acid composition in humans. Seven male subjects performed endurance training of the knee extensors of one leg for 4 wk. The other leg served as a control. Before, after 4 days, and after 4 wk, muscle biopsies were obtained from the vastus lateralis. After 4 wk, the phospholipid fatty acid contents of oleic acid 18:1(n-9) and docosahexaenoic acid 22:6(n-3) were significantly higher in the trained (10.9 ± 0.5% and 3.2 ± 0.4% of total fatty acids, respectively) than the untrained leg (8.8 ± 0.5% and 2.6 ± 0.4%, P < 0.05). The ratio between n-6 and n-3 fatty acids was significantly lower in the trained (11.1 ± 0.9) than the untrained leg (13.1 ± 1.2, P < 0.05). In contrast, training did not affect muscle triacylglycerol fatty acid composition. Citrate synthase activity was increased by 17% in the trained compared with the untrained leg ( P < 0.05). In this model, diet plays a minimal role, as the influence of dietary intake is similar on both legs. Regular exercise training per se influences the phospholipid fatty acid composition of muscle membranes but has no effect on the composition of fatty acids stored in triacylglycerols within the muscle.


2019 ◽  
Author(s):  
Manja Zec ◽  
Ljiljana Stojković ◽  
Milica Zeković ◽  
Biljana Pokimica ◽  
Maja Živković ◽  
...  

Abstract Background High omega-6/omega-3 intake ratio in westernized world is of concern. FADS genes variants are associated with plasma long-chain polyunsaturated fatty acids (LC-PUFA) in diverse ethnicities and might modulate plasma omega-6/omega-3 net balance. Therefore, the objective of this study was to evaluate the relationships between FADS genetic variants with dietary fat and macronutrient intake, plasma phospholipid fatty acid profile, estimated plasma desaturase activity and cardiometabolic risk factors, in a sample of Serbian subjects.Methods Non-smoking adult volunteers (>28 years), free of acute or chronic disease were included. Food and nutrient data were compiled through 24h recalls for non-consecutive days. Plasma phospholipid fatty acid content was assessed by gas-chromatography. Selection of FADS2 variants (rs174593, rs174616 and rs174576) was based on its positional and functional aspect, and evidence-based data. Genotyping was performed by using Real-Time PCR. Estimated desaturase activities were calculated as conversion rates towards LC-PUFA in omega-6 pathway. Multivariable-adjusted general linear were applied and the contribution of minor alleles to the variability of physiological parameters was analyzed by multivariable hierarchical multiple regression models.Results Sample included 34 men and 54 women, mean age=40±7years, with 70% being overweight (BMI>25). Minor allele frequencies were 33%, 36% and 51% for rs174593, rs174576 and rs174616, respectively, in line with other populations. None of the three variants was associated with food or nutrient intake, serum lipids, or obesity (p>0.05). Irrespective of gender, age, total daily polyunsaturated/saturated fatty acid intake and obesity, rs174593, rs174616 and rs174576 were associated with lower arachidonic acid (AA, C20:4 n-6, p<0.001) and estimated desaturase-5 activity (p<0.001) in plasma phospholipids. The rs174576 associations with AA withstood multiple testing and additional adjustments for other variants.Conclusion We observed inverse associations between FADS2 variants and plasma phospholipid AA but not omega-3 fatty acids in a sample of Serbian adults, and larger cohorts should confirm the associations. In our study FADS2 rs174576 exhibited the strongest associations, and future gene-dietary studies with varying omega-6/omega-3 intake should validate its suitability for precision nutrition strategies aimed at PUFA recommendations in Serbian population.Trial registration This is a cross-sectional study, forming part of larger intervention study registered at ClinicalTrials.gov as NCT02800967.


Sign in / Sign up

Export Citation Format

Share Document