Differential cerebral cortex transcriptomes of baboon neonates consuming moderate and high docosahexaenoic acid formulas.

Over the past 100 years, changes in the food supply in Western nations have resulted in alterations in dietary fatty acid consumption, leading to a dramatic increase in the ratio of omega-6 (omega6) to omega3 polyunsaturated fatty acids (PUFA) in circulation and in tissues. Increased omega6/omega3 ratios are hypothesized to increase inflammatory mediator production, leading to higher incidence of inflammatory diseases, and may impact inflammatory gene expression. To determine the effect of reducing the omega6/omega3 ratio on expression of inflammatory pathway genes in mononuclear cells, healthy humans were placed on a controlled diet for 1 week, then given fish oil and borage oil for an additional 4 weeks. Serum and neutrophil fatty acid composition and ex vivo leukotriene B(4) production from stimulated neutrophils were measured at the start and end of the supplementation period and after a 2-week washout. RNA was isolated from mononuclear cells and expression of PI3K, Akt, NFkappaB, and inflammatory cytokines was measured by real-time PCR. A marked increase was seen in serum and neutrophil levels of long-chain omega3 PUFA concomitant with a reduction in the omega6/omega3 PUFA ratio (40%). The ex vivo capacity of stimulated neutrophils to produce leukotriene B(4) was decreased by 31%. Expression of PI3Kalpha and PI3Kgamma and the quantity of PI3Kalpha protein in mononuclear cells was reduced after supplementation, as was the expression of several proinflammatory cytokines. These data reveal that PUFA may exert their clinical effects via their capacity to regulate the expression of signal transduction genes and genes for proinflammatory cytokines.

Omega-3 long chain fatty acid synthesis is regulated more by substrate levels than gene expression

Long chain polyunsaturated fatty acids (LCPUFA) namely arachidonic acid (ARA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3) are highly concentrated in the phospholipid bilayer of biologically active brain and retinal neural membranes and are important in phototransduction and neuronal function. The rationale for adding these LCPUFA to infant formula (IF) was primarily because of their presence in large quantities in the retina and brain and in human milk. In addition, infants fed IF containing LCPUFA and breastfed infants have comparable ARA and DHA levels in red cell and plasma, in contrast to the lower ARA and DHA levels in those fed IF containing only the essential fatty acids: linoleic (LA, 18:2n-6) and linolenic (LNA, 18:3n-3), the precursors to ARA and DHA, respectively. However, functional benefits in particular visual or neural development from IF containing LCPUFA remains controversial. Potential for excessive and/or imbalanced intake of n-6 and n-3 fatty acids exists with increasing fortification of LCPUFA to infant foods other than IF.

Beyin, retina ve diğer sinir dokuları uzun zincirli çoklu doymamış yağ asitlerinden (UZÇDYA) zengindir. Birçok klinik ve epidemiyolojik çalışma ile omega-3 UZÇDYA’ların çocukluk çağındaki nöral gelişim üzerine olumlu etkileri olduğu kanıtlanmıştır. Uzun zincirli ÇDYA’lar, diyetle alımları yeterli olduğu sürece temel elzem yağ asitlerinden endojen olarak sentezlenebilirler. Aynı zamanda, et, balık, yumurta, karaciğer ve süt ürünleri gibi proteinden zengin besinler eikosapentaenoik asit (EPA) ve dokosaheksaenoik asit (DHA) gibi UZÇDYA’ların en belirgin diyetsel kaynaklarıdır. Bununla birlikte, klasik fenilketonürili (FKÜ) hastalar yüksek plazma fenilalanin konsantrasyonları ve nörolojik hasarı önlemek için diyet protein alımında sıkı ve ömür boyu süren bir sınırlamaya ihtiyaç duyarlar. Bu katı metabolik kontrol sadece düşük miktarda vitamin ve mineral sağlamakla kalmaz, genellikle doymuş yağ asitleri ve ÇDYA’ların da düşük miktarda alınmasına neden olur. Bu nedenle, FKÜ’lü hastalar sağlıklı kontrollerle karşılaştırıldığında UZÇDYA alımları daha az olmakta ve daha düşük plazma ve eritrosit UZÇDYA konsantrasyonlarına sahip olmaktadırlar. Bebeklik ve çocukluk döneminde, UZÇDYA’lar normal nörogelişim için önemlidir. Yetersizliği, okul öncesi ve okul çağındaki FKÜ’lü çocuklarda erken dönemde saptanabilen merkezi sinir sistemi işlev bozukluklarına katkıda bulunabilir. Ayrıca, UZÇDYA yetersizliğinin kronik nörolojik, inflamatuvar ve metabolik bozukluklara neden olabileceği de ileri sürülmektedir. Diğer taraftan, randomize kontrollü çalışmalardan elde edilen veriler, FKÜ’lü hastalardaki UZÇDYA durumunun diyet takviyesi ile iyileştirilebileceğini önermektedir. Bu derleme yazıda, fenilalaninden kısıtlı diyetler ile UZÇDYA arasındaki ilişki incelenmiş ve FKÜ’lü hastalar için UZÇDYA’ların önemi ele alınmıştır.

The reliance of the aquafeed industry on marine resources has to be reduced by innovative approaches in fish nutrition. Thus, a three-factorial approach (fish oil reduced diet, phytochemical genistein, and temperature reduction) was chosen to investigate the interaction of effects on growth performance and tissue omega-3 long chain polyunsaturated fatty acid (LC-PUFA) levels in juvenile sea bream (Sparus aurata, 12.5 ± 2.2 g). Genistein is a phytoestrogen with estrogen-like activity and thus LC-PUFA increasing potential. A decrease in the rearing temperature was chosen based on the positive effects of low temperature on fish lipid quality. The experimental diets were reduced in marine ingredients and had a fish oil content of either 6% dry matter (DM; F6: positive control) or 2% DM (F2: negative control) and were administered in the plain variant or with inclusion of 0.15% DM genistein (F6 + G and F2 + G). The feeding trial was performed simultaneously at 23°C and 19°C. The results indicated that solely temperature had a significant effect on growth performance and whole body nutrient composition of sea bream. Nevertheless, the interaction of all three factors significantly affected the fatty acid compositions of liver and fillet tissue. Most importantly, they led to a significant increase by 4.3% of fillet LC-PUFA content in sea bream fed with the diet F6 + G in comparison to control fish fed diet F6, when both groups were held at 19°C. It is hypothesized that genistein can act via estrogen-like as well as other mechanisms and that the dietary LC-PUFA content may impact its mode of action. Temperature most likely exhibited its effects indirectly via altered growth rates and metabolism. Although effects of all three factors and of genistein in particular were only marginal, they highlight a possibility to utilize the genetic capacity of sea bream to improve tissue lipid quality.

A longitudinal analysis of prenatal exposure to methylmercury and fatty acids in the Seychelles

Cytochrome P450 oxidase 2J inhibition suppresses choroidal neovascularization in mice

Vegetable oils (VO) are possible substitutes for fish oil in aquafeeds but their use is limited by their lack of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA). However, oilseed crops can be modified to produce n-3 LC-PUFA such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, representing a potential option to fill the gap between supply and demand of these important nutrients. Camelina sativa was metabolically engineered to produce a seed oil with around 15% total n-3 LC-PUFA to potentially substitute for fish oil in salmon feeds. Post-smolt Atlantic salmon (Salmo salar) were fed for 11-weeks with one of three experimental diets containing either fish oil (FO), wild-type Camelina oil (WCO) or transgenic Camelina oil (DCO) as added lipid source to evaluate fish performance, nutrient digestibility, tissue n-3 LC-PUFA, and metabolic impact determined by liver transcriptome analysis. The DCO diet did not affect any of the performance or health parameters studied and enhanced apparent digestibility of EPA and DHA compared to the WCO diet. The level of total n-3 LC-PUFA was higher in all the tissues of DCO-fed fish than in WCO-fed fish with levels in liver similar to those in fish fed FO. Endogenous LC-PUFA biosynthetic activity was observed in fish fed both the Camelina oil diets as indicated by the liver transcriptome and levels of intermediate metabolites such as docosapentaenoic acid, with data suggesting that the dietary combination of EPA and DHA inhibited desaturation and elongation activities. Expression of genes involved in phospholipid and triacylglycerol metabolism followed a similar pattern in fish fed DCO and WCO despite the difference in n-3 LC-PUFA contents.

IntroductionThe pro-inflammatory status of cystic fibrosis (CF) patients promotes pulmonary colonization with opportunist and pathogenic bacteria, which is favored by a sticky mucus. Oral supplementation with (n-3) long chain polyunsaturated fatty acids (LC-PUFA) has shown anti-inflammatory effects. The aim of this study was to demonstrate the positive effects of a long-term diet enriched in (n-3) LC-PUFA on the lungs of Cftr F508del mice.Materials and methodsBreeding CftrΔF508del/+ mice received a control diet or a diet enriched in (n-3) LC-PUFA for 5 weeks before mating, gestation and lactation. After weaning, the offspring were given the same diet as their mother until post-natal day 60. The effects of (n-3) LC-PUFA supplementation on the lungs were evaluated in homozygous Cftr F508del mice and their wild-type littermates after acute lung inflammation induced by Pseudomonas aeruginosa lipopolysaccharide (LPS) inhalation.Results(n-3) LC-PUFA enrichment of mothers contributes to enrichment of mammary milk and cell membrane of suckling pups. Cftr F508del mice exhibited growth retardation and lung damage with collapsed alveoli, hyperplasia of bronchial epithelial cells and inflammatory cell infiltration. The (n-3) LC-PUFA diet corrected the growth delay of Cftr F508del mice and decreased hyperplasia of bronchial epithelial cells. Besides decreasing metaplasia of Club cells after LPS inhalation, (n-3) LC-PUFA modulated lung inflammation and restricted lung damage.ConclusionLong-term (n-3) LC-PUFA supplementation shows moderate benefits to the lungs of Cftr F508del mice.

Microorganisms that generate and accumulate omega-3 long chain polyunsaturated fatty acid have acquired protagonism in the last decade. Omega-3 rich diets have showed multiple positive effects in clinical and nutritional studies. Marine and freshwater eukaryotic microorganism, autotrophic and heterotrophic, showed interesting yields and are good candidates to launch an industrial bioprocess. Docosahexaenoic acid (DHA) is typically the main goal. But other valuable fatty acids can be obtained as well, as eicosapentaenoic acid (EPA), alpha-linolenic acid (ALA) or arachidonic acid (AA). Currently the primary source of DHA is fish-oil, which carries bioaccumulated persistent organic pollutants (POP). A new and clean source of omega-3 oils may be highly interesting due to the growing number of clinical studies linking positive health effects to omega-3 rich diets. These studies have proofed equivalent positive effects using fish oil and algae oil. Long chain polyunsaturated fatty acids (LC-PUFAs) are bioactive lipids essential for human beings. PUFAs are poorly synthesized in superior animals, so basically LC- PUFAs are obtained from certain fish and plants. These fatty acids are ingested in reasonable amounts, as part of the daily diet. In the last couple of decades supplementation in food matrices as enriched foods (milk and other dairy products, eggs, cookies, fruit juice or olives) has become popular. These products are considered functional foods and LC-PUFAs nutraceuticals, with an increasing interest from the society. Many scientific-clinical studies have demonstrated different positive effects of such bioactive

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk.

Diets high in n-3 long chain polyunsaturated fatty acids (LCPUFA) may modulate the development of IgE-mediated allergic disease and have been proposed as a possible allergy prevention strategy. The aim of this study was to determine whether n-3 LCPUFA supplementation of pregnant women reduces IgE-mediated allergic disease in their children. Follow-up of children (n = 706) at hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome randomized controlled trial. The intervention group (n = 368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks' gestation until birth; the control group (n = 338) received matched vegetable oil capsules without n-3 LCPUFA. The diagnosis of allergic disease was made during medical assessments at 1 and 3 years of age. No differences were seen in the overall percentage of children with IgE-mediated allergic disease in the first 3 years of life between the n-3 LCPUFA and control groups (64/368 (17.3%) vs 76/338 (22.6%); adjusted relative risk 0.78; 95% CI 0.58-1.06; P = 0.11). Eczema was the most common allergic disease; 13.8% of children in the n-3 LCPUFA group had eczema with sensitization compared with 19.0% in the control group (adjusted relative risk 0.75; 95% CI 0.53-1.05; P = 0.10). Overall, n-3 LCPUFA supplementation during pregnancy did not significantly reduce IgE-associated allergic disease in the first 3 years of life. Further studies should examine whether the nonsignificant reductions in IgE-associated allergies are of clinical and public health significance.

To establish the levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in both plasma and erythrocytes of maternal and cord blood as well as in breast milk of mothers delivering babies at term. A total of 148 mothers delivering babies at term were recruited from Bharati Medical Hospital, Pune, India. Levels of DHA and AA in both plasma and erythrocyte were higher in cord blood compared to levels in maternal blood (P<0.001). Maternal plasma and erythrocyte DHA levels had a positive association with the respective levels in cord blood (P<0.001). However, such an association was not seen for AA levels. Maternal plasma omega 3 and omega 6 fatty acids were positively associated with the respective milk fatty acids (P<0.01). Our results indicate that milk long-chain polyunsaturated fatty acids (LCPUFA) status reflects the concentrations of maternal LCPUFA in women delivering babies at term. Improving the maternal LCPUFA status throughout pregnancy and lactation may improve the milk LCPUFA status and ultimately benefit the infant.

Associations of birth weight with serum long chain polyunsaturated fatty acids in adolescents; the HELENA study

We reported previously that infants who were fed an unsupplemented formula or one with DHA or with both DHA and ARA through 12 months or were breastfed showed no differences in mental and motor development, but those who were fed DHA without ARA had lower vocabulary scores on a standardized, parent-report instrument at 14 months of age when compared with infants who were fed the unsupplemented formula or who were breastfed. When the infants were reassessed at 39 months using age-appropriate tests of receptive and expressive language as well as IQ, visual-motor function and visual acuity, no differences among the formula groups or between the formula and breastfed groups were found. The 14-month observation thus may have been a transient effect of DHA (without ARA) supplementation on early vocabulary development or may have occurred by chance. The absence of differences in growth achievement adds to the evidence that DHA with or without ARA supports normal growth in full-term infants. In conclusion, adding both DHA and ARA when supplementing infant formulas with long-chain polyunsaturated fatty acids supports visual and cognitive development through 39 months.