n-3 long-chain PUFA promote antibacterial and inflammation-resolving effects in Mycobacterium tuberculosis-infected C3HeB/FeJ mice, dependent on fatty acid status.

Non-resolving inflammation is characteristic of tuberculosis (TB). Given their inflammation-resolving properties, n-3 long-chain PUFA (n-3 LCPUFA) may support TB treatment. This research aimed to investigate the effects of n-3 LCPUFA on clinical and inflammatory outcomes of Mycobacterium tuberculosis-infected C3HeB/FeJ mice with either normal or low n-3 PUFA status before infection. Using a two-by-two design, uninfected mice were conditioned on either an n-3 PUFA-sufficient (n-3FAS) or -deficient (n-3FAD) diet for 6 weeks. One week post-infection, mice were randomised to either n-3 LCPUFA supplemented (n-3FAS/n-3+ and n-3FAD/n-3+) or continued on n-3FAS or n-3FAD diets for 3 weeks. Mice were euthanised and fatty acid status, lung bacterial load and pathology, cytokine, lipid mediator and immune cell phenotype analysed. n-3 LCPUFA supplementation in n-3FAS mice lowered lung bacterial loads (P = 0·003), T cells (P = 0·019), CD4+ T cells (P = 0·014) and interferon (IFN)-γ (P < 0·001) and promoted a pro-resolving lung lipid mediator profile. Compared with n-3FAS mice, the n-3FAD group had lower bacterial loads (P = 0·037), significantly higher immune cell recruitment and a more pro-inflammatory lipid mediator profile, however, significantly lower lung IFN-γ, IL-1α, IL-1ß and IL-17, and supplementation in the n-3FAD group provided no beneficial effect on lung bacterial load or inflammation. Our study provides the first evidence that n-3 LCPUFA supplementation has antibacterial and inflammation-resolving benefits in TB when provided 1 week after infection in the context of a sufficient n-3 PUFA status, whilst a low n-3 PUFA status may promote better bacterial control and lower lung inflammation not benefiting from n-3 LCPUFA supplementation.

Fish oil supplementation may improve attention, working memory and attention-deficit/hyperactivity disorder symptoms in adults with autism spectrum disorder: a randomised crossover trial.

Marine n-3 fatty acids (n-3LCPUFA) have shown neurocognitive benefits in children with attention-deficit/hyperactivity disorder (ADHD), but few trials have examined effects in adults with autism spectrum disorder (ASD). We explored, if n-3LCPUFA affect cognitive functions in adults with ASD, and if effects are modified by comorbid ADHD. In a 2 × 4 week crossover study, twenty-six participants were randomised to sequence of supplementation with fish oil (FO, 5·2 g/d n-3PUFA) and safflower oil (SO). At baseline and after each period, we measured primary outcomes: attention (d2-test) and spatial working memory (Corsi test) and secondary outcomes: flexibility (Stroop word-colour test), ADHD symptoms (Conners scales), executive functions (Behavioural Inventory of Executive Function) and social behaviour (Social Responsiveness Scale). The dropout rate was 15 %. Compliance was 94 % and correlated with whole-blood n-3LCPUFA. Corsi scores improved by ∼0·3 × sd (P = 0·032) after FO v. SO, and the odds for d2 errors were 30 % lower (P = 0·016), which was supported by improved Conners scores of attention (P = 0·023). Improvement in Conners ADHD symptom score was limited to participants with ADHD (-3·5(-6·0; -1·0), n 10 v. -0·2(-2·5;2·2), n 11 without ADHD, Pinteraction = 0·096), who also improved their behavioural regulation index by 0·3 × sd after FO (Pinteraction = 0·016). Participants without ADHD gained most in d2 test performance (OR = 0·4(0·2;0·7) v. 0·9(0·6;1·3) in those with ADHD, Pinteraction = 0·002), but their executive function score was exacerbated after FO (5·9(0·0,11·8), Pinteraction = 0·039). Our results did not show any effects on ASD symptoms, but suggest that FO may improve attention and working memory in adults with ASD and ameliorate ADHD symptoms in those with comorbid ADHD.

PPARγ regulates fabp4 expression to increase DHA content in golden pompano (Trachinotus ovatus) hepatocytes.

N-3 long-chain (≥C20) PUFA (LC-PUFA) are vital fatty acids for fish and humans. As a main source of n-3 LC-PUFA for human consumers, the n-3 LC-PUFA content of farmed fish is important. Previously, we identified fatty acid-binding protein (fabp)-4 as a candidate gene for regulating the n-3 LC-PUFA content. Herein, we further assessed the role of fabp4 in this process. First, a 2059 bp promoter sequence of fabp4 in Trachinotus ovatus was cloned and, using progressive deletion, determined -2006 bp to -1521 bp to be the core promoter sequence. The PPAR-γ binding sites were predicted to occur in this region. A luciferase reporter assay showed that the promoter activity of fabp4 decreased following mutation of the PPARγ binding site and that PPARγ increased the fabp4 promoter activity in a dose-dependent manner, implying that T. ovatus fabp4 is a target of PPARγ. The overexpression of fabp4 or PPARγ increased the DHA content in hepatocytes, whereas suppression of their expression diminished this effect, suggesting that both fabp4 and PPARγ play an active role in regulating DHA content. Moreover, the inhibition of fabp4 attenuated the increase in PPARγ-mediated DHA content, and the overexpression of fabp4 alleviated this effect. Collectively, our findings indicated that fabp4, which is controlled by PPARγ, plays an important role in DHA content regulation. The new regulation axis can be considered a promising novel target for increasing the n-3 LC-PUFA content in T. ovatus.

Dietary lipid and n-3 long-chain PUFA levels impact growth performance and lipid metabolism of juvenile mud crab, Scylla paramamosain.

An 8-week feeding trial was conducted to evaluate the effects of dietary n-3 LC-PUFA levels on growth performance, tissue fatty acid profiles and relative expression of genes involved in the lipid metabolism of mud crab (Scylla paramamosain). Ten isonitrogenous diets were formulated to contain five n-3 LC-PUFA levels at 7 and 12 % dietary lipid levels. The highest weight gain and specific growth rate were observed in crabs fed the diets with 19·8 and 13·2 mg/g n-3 LC-PUFA at 7 and 12 % lipid, respectively. Moisture and lipid contents in hepatopancreas and muscle were significantly influenced by dietary n-3 LC-PUFA at the two lipid levels. The DHA, EPA, n-3 LC-PUFA contents and n-3:n-6 PUFA ratio in hepatopancreas and muscle significantly increased as dietary n-3 LC-PUFA levels increased at both lipid levels. The expression levels of -6 fatty acyl desaturase and acyl-CoA oxidase in hepatopancreas increased significantly, and expression levels of fatty acid synthase, carnitine palmitoyltransferase I and hormone-sensitive TAG lipase were down-regulated, with increased dietary n-3 LC-PUFA regardless of lipid level. Based on weight gain, n-3 LC-PUFA requirements of S. paramamosain were estimated to be 20·1 and 12·7 mg/g of diet at 7 and 12 % dietary lipid, respectively. Overall, dietary lipid level influenced lipid metabolism, and purified, high-lipid diets rich in palmitic acid reduced the n-3 LC-PUFA requirement of juvenile mud crab.

The impact of EPA and DHA on ceramide lipotoxicity in the metabolic syndrome.

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including obesity, insulin resistance (IR) and dyslipidaemia. Consumption of a high-fat diet (HFD) enriched in SFA leads to the accumulation of ceramide (Cer), the central molecule in sphingolipid metabolism. Elevations in plasma and tissue Cer are found in obese individuals, and there is evidence to suggest that Cer lipotoxicity contributes to the MetS. EPA and DHA have shown to improve MetS parameters including IR, inflammation and hypertriacylglycerolaemia; however, whether these improvements are related to Cer is currently unknown. This review examines the potential of EPA and DHA to improve Cer lipotoxicity and MetS parameters including IR, inflammation and dyslipidaemia in vitro and in vivo. Current evidence from cell culture and animal studies indicates that EPA and DHA attenuate palmitate- or HFD-induced Cer lipotoxicity and IR, whereas evidence in humans is greatly lacking. Overall, there is intriguing potential for EPA and DHA to improve Cer lipotoxicity and related MetS parameters, but more research is warranted.

Long-chain PUFA profiles in parental diets induce long-term effects on growth, fatty acid profiles, expression of fatty acid desaturase 2 and selected immune system-related genes in the offspring of gilthead seabream.

The present study investigated the effects of nutritional programming through parental feeding on offspring performance and expression of selected genes related to stress resistance in a marine teleost. Gilthead seabream broodstock were fed diets containing various fish oil (FO)/vegetable oil ratios to determine their effects on offspring performance along embryogenesis, larval development and juvenile on-growing periods. Increased substitution of dietary FO by linseed oil (LO) up to 80 % LO significantly reduced the total number of eggs produced by kg per female per spawn. Moreover, at 30 d after hatching, parental feeding with increasing LO up to 80 % led to up-regulation of the fatty acyl desaturase 2 gene (fads2) that was correlated with the increase in conversion rates of related PUFA. Besides, cyclo-oxygenase 2 (cox2) and TNF-α (tnf-α) gene expression was also up-regulated by the increase in LO in broodstock diets up to 60 or 80 %, respectively. When 4-month-old offspring were challenged with diets having different levels of FO, the lowest growth was found in juveniles from broodstock fed 100 % FO. An increase in LO levels in the broodstock diet up to 60LO raised LC-PUFA levels in the juveniles, regardless of the juvenile's diet. The results showed that it is possible to nutritionally programme gilthead seabream offspring through the modification of the fatty acid profiles of parental diets to improve the growth performance of juveniles fed low FO diets, inducing long-term changes in PUFA metabolism with up-regulation of fads2 expression. The present study provided the first pieces of evidence of the up-regulation of immune system-related genes in the offspring of parents fed increased FO replacement by LO.

Endogenous biosynthesis of n-3 long-chain PUFA in Atlantic salmon.

A more efficient utilisation of marine-derived sources of dietary n-3 long-chain PUFA (n-3 LC PUFA) in cultured Atlantic salmon (Salmo salar L.) could be achieved by nutritional strategies that maximise endogenous n-3 LC PUFA synthesis. The objective of the present study was to quantify the extent of n-3 LC PUFA biosynthesis and the resultant effect on fillet nutritional quality in large fish. Four diets were manufactured, providing altered levels of dietary n-3 substrate, namely, 18 : 3n-3, and end products, namely, 20 : 5n-3 and 22 : 6n-3. After 283 d of feeding, fish grew in excess of 3000 g and no differences in growth performance or biometrical parameters were recorded. An analysis of fatty acid composition and in vivo metabolism revealed that endogenous production of n-3 LC PUFA in fish fed a diet containing no added fish oil resulted in fillet levels of n-3 LC PUFA comparable with fish fed a diet with added fish oil. However, this result was not consistent among all treatments. Another major finding of this study was the presence of abundant dietary n-3 substrate, with the addition of dietary n-3 end product (i.e. fish oil) served to increase final fillet levels of n-3 LC PUFA. Specifically, preferential ß-oxidation of dietary C18 n-3 PUFA resulted in conservation of n-3 LC PUFA from catabolism. Ultimately, this study highlights the potential for endogenous synthesis of n-3 LC PUFA to, partially, support a substantial reduction in the amount of dietary fish oil in diets for Atlantic salmon reared in seawater.

Non-dietary factors associated with n-3 long-chain PUFA levels in humans - a systematic literature review.

Numerous health benefits are attributed to the n-3 long-chain PUFA (n-3 LCPUFA); EPA and DHA. A systematic literature review was conducted to investigate factors, other than diet, that are associated with the n-3 LCPUFA levels. The inclusion criteria were papers written in English, carried out in adult non-pregnant humans, n-3 LCPUFA measured in blood or tissue, data from cross-sectional studies, or baseline data from intervention studies. The search revealed 5076 unique articles of which seventy were included in the qualitative synthesis. Three main groups of factors potentially associated with n-3 LCPUFA levels were identified: (1) unmodifiable factors (sex, genetics, age), (2) modifiable factors (body size, physical activity, alcohol, smoking) and (3) bioavailability factors (chemically bound form of supplements, krill oil v. fish oil, and conversion of plant-derived α-linolenic acid (ALA) to n-3 LCPUFA). Results showed that factors positively associated with n-3 LCPUFA levels were age, female sex (women younger than 50 years), wine consumption and the TAG form. Factors negatively associated with n-3 LCPUFA levels were genetics, BMI (if erythrocyte EPA and DHA levels are <5·6 %) and smoking. The evidence for girth, physical activity and krill oil v. fish oil associated with n-3 LCPUFA levels is inconclusive. There is also evidence that higher ALA consumption leads to increased levels of EPA but not DHA. In conclusion, sex, age, BMI, alcohol consumption, smoking and the form of n-3 LCPUFA are all factors that need to be taken into account in n-3 LCPUFA research.

Modulation of aquaporin gene expression by n-3 long-chain PUFA lipid structures in white and brown adipose tissue from hamsters.

EPA (20 : 5n-3) and DHA (22 : 6n-3) fatty acids have weight-reducing properties with physiological activity depending on their molecular structure - that is, as TAG or ethyl esters (EE). Aquaporins (AQP) are membrane protein channels recognised as important players in fat metabolism, but their differential expression in white adipose tissue (WAT) and brown adipose tissue (BAT), as well as their modulation by dietary n-3 long-chain PUFA (LCPUFA) such as EPA and DHA, has never been investigated. In this study, the transcriptional profiles of AQP3, AQP5, AQP7 and selected lipid markers of WAT (subcutaneous and visceral) and BAT (interscapular) from hamsters fed diets containing n-3 LCPUFA in different lipid structures such as fish oil (FO, rich in EPA and DHA in the TAG form) and FO-EE (rich in EPA and DHA in the EE form) were used and compared with linseed oil (LSO) as the reference group. A clear effect of fat depot was observed for AQP3 and leptin (LEP), with the lowest values of mRNA found in BAT relative to WAT. The opposite occurred for PPARα. AQP7 was affected by diet, with FO-fed hamsters having higher mRNA levels compared with LSO-fed hamsters. The relative gene expression of AQP5, adiponectin (ADIPO), GLUT4 and PPARγ was influenced by both fat tissue and diet. Taken together, our results revealed a differential expression profile of AQP and some markers of lipid metabolism in both WAT and BAT in response to feeding n-3 LCPUFA in two different structural formats: TAG v. EE.

Association of oily fish intake, sex, age, BMI and APOE genotype with plasma long-chain n-3 fatty acid composition.

n-3 Fatty acids are associated with better cardiovascular and cognitive health. However, the concentration of EPA, DPA and DHA in different plasma lipid pools differs and factors influencing this heterogeneity are poorly understood. Our aim was to evaluate the association of oily fish intake, sex, age, BMI and APOE genotype with concentrations of EPA, DPA and DHA in plasma phosphatidylcholine (PC), NEFA, cholesteryl esters (CE) and TAG. Healthy adults (148 male, 158 female, age 20-71 years) were recruited according to APOE genotype, sex and age. The fatty acid composition was determined by GC. Oily fish intake was positively associated with EPA in PC, CE and TAG, DPA in TAG, and DHA in all fractions (P≤0·008). There was a positive association between age and EPA in PC, CE and TAG, DPA in NEFA and CE, and DHA in PC and CE (P≤0·034). DPA was higher in TAG in males than females (P<0·001). There was a positive association between BMI and DPA and DHA in TAG (P<0·006 and 0·02, respectively). APOE genotype×sex interactions were observed: the APOE4 allele associated with higher EPA in males (P=0·002), and there was also evidence for higher DPA and DHA (P≤0·032). In conclusion, EPA, DPA and DHA in plasma lipids are associated with oily fish intake, sex, age, BMI and APOE genotype. Such insights may be used to better understand the link between plasma fatty acid profiles and dietary exposure and may influence intake recommendations across population subgroups.

Oil from transgenic Camelina sativa containing over 25 % n-3 long-chain PUFA as the major lipid source in feed for Atlantic salmon (Salmo salar).

Facing a bottleneck in the growth of aquaculture, and a gap in the supply and demand of the highly beneficial n-3 long-chain PUFA (LC-PUFA), sustainable alternatives to traditional marine-based feeds are required. Therefore, in the present trial, a novel oil obtained from a genetically engineered oilseed crop, Camelina sativa, that supplied over 25 % n-3 LC-PUFA was tested as a sole dietary-added lipid source in Atlantic salmon (Salmo salar) feed. Three groups of fish were fed three experimental diets for 12 weeks with the same basal composition and containing 20 % added oil supplied by either a blend of fish oil and rapeseed oil (1:3) (COM) reflecting current commercial formulations, wild-type Camelina oil (WCO) or the novel transgenic Camelina oil (TCO). There were no negative effects on the growth, survival rate or health of the fish. The whole fish and flesh n-3 LC-PUFA levels were highest in fish fed TCO, with levels more than 2-fold higher compared with those of fish fed the COM and WCO diets, respectively. Diet TCO had no negative impacts on the evaluated immune and physiological parameters of head kidney monocytes. The transcriptomic responses of liver and mid-intestine showed only mild effects on metabolism genes. Overall, the results clearly indicated that the oil from transgenic Camelina was highly efficient in supplying n-3 LC-PUFA providing levels double that obtained with a current commercial standard, and similar to those a decade ago before substantial dietary fishmeal and oil replacement.

Effects of the flavonol quercetin and α-linolenic acid on n-3 PUFA status in metabolically healthy men and women: a randomised, double-blinded, placebo-controlled, crossover trial.

Increased dietary intake and tissue status of the long-chain n-3 PUFA, EPA and DHA, is associated with cardiovascular benefits. Epidemiological and animal studies suggest that concomitant nutritive intake of flavonoids may increase the conversion of α-linolenic acid (ALA) to longer-chain n-3 fatty acids EPA and DHA. We investigated the effects of increased ALA intake on fatty acid composition of serum phospholipids and erythrocytes in metabolically healthy men and women and whether fatty acid profiles and ALA conversion were affected by regular quercetin intake or sex. Subjects (n 74) were randomised to receive at least 3·3 g/d ALA with either 190 mg/d quercetin (ALA+quercetin) or placebo (ALA+placebo) in a double-blinded, placebo-controlled, crossover trial with 8-week intervention periods separated by an 8-week washout period. A total of seven subjects dropped out for personal reasons. Data from the remaining sixty-seven subjects (thirty-four males and thirty-three females) were included in the analysis. Both interventions significantly increased serum phospholipid ALA (ALA+placebo: +69·3 %; ALA+quercetin: +55·8 %) and EPA (ALA+placebo: +37·3 %; ALA+quercetin: +25·5 %). ALA + quercetin slightly decreased DHA concentration by 9·3 %. Erythrocyte ALA and EPA significantly increased with both interventions, whereas DHA decreased. Fatty acid composition did not differ between sexes. We found no effect of quercetin. Intake of 3·6 g/d ALA over an 8-week period resulted in increased ALA and EPA, but not DHA, in serum phospholipids and erythrocytes. Neither quercetin supplementation nor sex affected the increment of ALA and relative proportions of n-3 PUFA in serum phospholipids and erythrocytes.

Genomics of lactation: role of nutrigenomics and nutrigenetics in the fatty acid composition of human milk.

Human milk covers the infant's nutrient requirements during the first 6 months of life. The composition of human milk progressively changes during lactation and it is influenced by maternal nutritional factors. Nowadays, it is well known that nutrients have the ability to interact with genes and modulate molecular mechanisms impacting physiological functions. This has led to a growing interest among researchers in exploring nutrition at a molecular level and to the development of two fields of study: nutrigenomics, which evaluates the influence of nutrients on gene expression, and nutrigenetics, which evaluates the heterogeneous individual response to nutrients due to genetic variation. Fatty acids are one of the nutrients most studied in relation to lactation given their biologically important roles during early postnatal life. Fatty acids modulate transcription factors involved in the regulation of lipid metabolism, which in turn causes a variation in the proportion of lipids in milk. This review focuses on understanding, on the one hand, the gene transcription mechanisms activated by maternal dietary fatty acids and, on the other hand, the interaction between dietary fatty acids and genetic variation in genes involved in lipid metabolism. Both of these mechanisms affect the fatty acid composition of human milk.

Cross-sectional association between serum concentrations of n-3 long-chain PUFA and depressive symptoms: results in Japanese community dwellers.

The effect of n-3 long-chain PUFA (n-3 LCPUFA) on depression in healthy subjects is unclear, and most of the previous studies have focused on populations eating Western diets with lower fish intake. The present study investigated the association between blood levels of n-3 LCPUFA and depressive symptoms in Japanese community dwellers with higher n-3 LCPUFA blood levels. A cross-sectional study was conducted from 2006 to 2008, including 1050 men and 1073 women aged 40 years or older from the National Institute for Longevity Sciences--the Longitudinal Study of Aging. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depressive symptoms. Multiple logistic regression analysis was performed to estimate the OR and 95% CI for a CES-D score ≥ 16. Serum concentrations of n-3 PUFA, but not n-6 PUFA, were inversely associated with depressive symptoms. Compared with the lowest quintile, the adjusted OR for serum EPA at the fourth and fifth quintiles were 0·55 (95% CI 0·35, 0·85) and 0·64 (95% CI 0·42, 0·98), respectively, and at the fifth quintile for DHA it was 0·58 (95% CI 0·37, 0·92), for the presence of depressive symptoms (P for trend=0·013 and 0·011, respectively). Serum levels of EPA and DHA were inversely associated with depressive symptoms in Japanese community dwellers with higher blood levels of n-3 LCPUFA, suggesting that n-3 LCPUFA intakes corresponding to higher levels in a Japanese population may have implications for a lower prevalence of depression.

Maternal fish oil supplementation during lactation is associated with reduced height at 13 years of age and higher blood pressure in boys only.

Dietary long-chain n-3 PUFA (n-3 LCPUFA) in infancy may have long-term effects on lifestyle disease risk. The present follow-up study investigated whether maternal fish oil (FO) supplementation during lactation affected growth and blood pressure in adolescents and whether the effects differed between boys and girls. Mother-infant pairs (n 103) completed a randomised controlled trial with FO (1·5 g/d n-3 LCPUFA) or olive oil (OO) supplements during the first 4 months of lactation; forty-seven mother-infant pairs with high fish intake were followed-up for 4 months as the reference group. We also followed-up 100 children with assessment of growth, blood pressure, diet by FFQ and physical activity by 7-d accelerometry at 13·5 (sd 0·4) years of age. Dried whole-blood fatty acid composition was analysed in a subgroup (n 49). At 13 years of age, whole-blood n-3 LCPUFA, diet, physical activity and body composition did not differ between the three groups. The children from the FO group were 3·4 (95 % CI 0·2, 6·6) cm shorter (P=0·035) than those from the OO group, and tended to have less advanced puberty (P=0·068), which explained the difference in height. There was a sex-specific effect on diastolic blood pressure (P sex×group=0·020), which was driven by a 3·9 (95 % CI 0·2, 7·5) mmHg higher diastolic blood pressure in the FO compared with the OO group among boys only (P=0·041). Our results indicate that early n-3 LCPUFA intake may reduce height in early adolescence due to a delay in pubertal maturation and increase blood pressure specifically in boys, thereby tending to counteract existing sex differences.

Fish oil supplementation from 9 to 18 months of age affects the insulin-like growth factor axis in a sex-specific manner in Danish infants.

Several studies have investigated the effects of fish oil (FO) on infant growth, but little is known about the effects of FO and sex on insulin-like growth factor-1 (IGF-1), the main regulator of growth in childhood. We explored whether FO v. sunflower oil (SO) supplementation from 9 to 18 months of age affected IGF-1 and its binding protein-3 (IGFBP-3) and whether the potential effects were sex specific. Danish infants (n 115) were randomly allocated to 5 ml/d FO (1·2 g/d n-3 long-chain PUFA (n-3 LCPUFA)) or SO. We measured growth, IGF-1, IGFBP-3 and erythrocyte EPA, a biomarker of n-3 LCPUFA intake and status, at 9 and 18 months. Erythrocyte EPA increased strongly with FO compared with SO (P<0·001). There were no effects of FO compared with SO on IGF-1 in the total population, but a sex × group interaction (P=0·02). Baseline-adjusted IGF-1 at 18 months was 11·1 µg/l (95% CI 0·4, 21·8; P=0·04) higher after FO compared with SO supplementation among boys only. The sex × group interaction was borderline significant in the model of IGFBP-3 (P=0·09), with lower IGFBP-3 with FO compared with SO among girls only (P=0·03). The results were supported by sex-specific dose-response associations between changes in erythrocyte EPA and changes in IGF-1 and IGFBP-3 (both P<0·03). Moreover, IGF-1 was sex specifically associated with BMI and length. In conclusion, FO compared with SO resulted in higher IGF-1 among boys and lower IGFBP-3 among girls. The potential long-term implications for growth and body composition should be investigated further.

Impact of fish oils on the outcomes of a mouse model of acute Pseudomonas aeruginosa pulmonary infection.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that causes pneumonia in immunocompromised humans and severe pulmonary damage in patients with cystic fibrosis. Imbalanced fatty acid incorporation in membranes, including increased arachidonic acid and decreased DHA concentrations, is known to play a critical role in chronic inflammation associated with bacterial infection. Other lipids, such as EPA and alkylglycerols, are also known to play a role in inflammation, particularly by stimulating the immune system, decreasing inflammation and inhibiting bacterial growth. In this context, the goal of the present study was to assess the effect of dietary DHA/EPA, in a 2:1 ratio, and alkylglycerols, as natural compounds extracted from oils of rays and chimeras, respectively, on the inflammatory reaction induced by P. aeruginosa pulmonary infection in mice. To this end, mice were fed with a control diet or isolipidic, isoenergetic diets prepared with oils enriched in DHA/EPA (2:1) or alkylglycerols for 5 weeks before the induction of acute P. aeruginosa lung infection by endotracheal instillation. In our model, DHA/EPA (2:1) significantly improved the survival of mice after infection, which was associated with the acceleration of bacterial clearance and the resolution of inflammation leading to the improvement of pulmonary injuries. By contrast, alkylglycerols did not affect the outcomes of P. aeruginosa infection. Our findings suggest that supplementation with ray oil enriched in DHA/EPA (2:1) can be considered as a preventive treatment for patients at risk for P. aeruginosa infection.

Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children: secondary analyses of the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study.

Fe and n-3 long-chain PUFA (n-3 LCPUFA) have both been associated with cognition, but evidence remains inconclusive in well-nourished school-aged children. In the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet (OPUS) School Meal Study, the 3-month intervention increased reading performance, inattention, impulsivity and dietary intake of fish and Fe. This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and, if so, explored how these changes correlated with the changes in cognitive performance. The study was a cluster-randomised cross-over trial comparing school meals with packed lunch (control). At baseline and after each treatment, we measured serum ferritin, whole-blood n-3 LCPUFA and Hb, and performance in reading, mathematics and d2-test of attention. Data were analysed using mixed models (n 726) and principal component analysis of test performances (n 644), which showed two main patterns: 'school performance' and 'reading comprehension'. The latter indicated that children with good reading comprehension were also more inattentive and impulsive (i.e. higher d2-test error%). The intervention improved 'school performance' (P=0·015), 'reading comprehension' (P=0·043) and EPA+DHA status 0·21 (95% CI 0·15, 0·27) w/w % (P<0·001), but it did not affect serum ferritin or Hb. At baseline, having small Fe stores was associated with poorer 'school performance' in girls, but with better 'reading comprehension' in both boys and girls. Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with 'school performance', suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect. These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study.

Comprehensive biometric, biochemical and histopathological assessment of nutrient deficiencies in gilthead sea bream fed semi-purified diets.

Seven isoproteic and isolipidic semi-purified diets were formulated to assess specific nutrient deficiencies in sulphur amino acids (SAA), n-3 long-chain PUFA (n-3 LC-PUFA), phospholipids (PL), P, minerals (Min) and vitamins (Vit). The control diet (CTRL) contained these essential nutrients in adequate amounts. Each diet was allocated to triplicate groups of juvenile gilthead sea bream fed to satiety over an 11-week feeding trial period. Weight gain of n-3 LC-PUFA, P-Vit and PL-Min-SAA groups was 50, 60-75 and 80-85 % of the CTRL group, respectively. Fat retention was decreased by all nutrient deficiencies except by the Min diet. Strong effects on N retention were found in n-3 LC-PUFA and P fish. Combined anaemia and increased blood respiratory burst were observed in n-3 LC-PUFA fish. Hypoproteinaemia was found in SAA, n-3 LC-PUFA, PL and Vit fish. Derangements of lipid metabolism were also a common disorder, but the lipodystrophic phenotype of P fish was different from that of other groups. Changes in plasma levels of electrolytes (Ca, phosphate), metabolites (creatinine, choline) and enzyme activities (alkaline phosphatase) were related to specific nutrient deficiencies in PL, P, Min or Vit fish, whereas changes in circulating levels of growth hormone and insulin-like growth factor I primarily reflected the intensity of the nutritional stressor. Histopathological scoring of the liver and intestine segments showed specific nutrient-mediated changes in lipid cell vacuolisation, inflammation of intestinal submucosa, as well as the distribution and number of intestinal goblet and rodlet cells. These results contribute to define the normal range of variation for selected biometric, biochemical, haematological and histochemical markers.

Dietary Fish Hydrolysate Improves Memory Performance Through Microglial Signature Remodeling During Aging.

Brain aging is characterized by a chronic low-grade inflammation, which significantly impairs cognitive function. Microglial cells, the immunocompetent cells of the brain, present a different phenotype, switching from a homeostatic signature (M0) to a more reactive phenotype called "MGnD" (microglial neurodegenerative phenotype), leading to a high production of pro-inflammatory cytokines. Furthermore, microglial cells can be activated by age-induced gut dysbiosis through the vagus nerve or the modulation of the peripheral immune system. Nutrients, in particular n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides, display powerful immunomodulatory properties, and can thus prevent age-related cognitive decline. The objective of this study was to investigate the effects of n-3 LC-PUFAs and low molecular weight peptides contained in a marine by-product-derived hydrolysate on microglial phenotypes and intestinal permeability and their consequences on cognition in mice. We demonstrated that the hydrolysate supplementation for 8 weeks prevented short- and long-term memory decline during aging. These observations were linked to the modulation of microglial signature. Indeed, the hydrolysate supplementation promoted homeostatic microglial phenotype by increasing TGF-ß1 expression and stimulated phagocytosis by increasing Clec7a expression. Moreover, the hydrolysate supplementation promoted anti-inflammatory intestinal pathway and tended to prevent intestinal permeability alteration occurring during aging. Therefore, the fish hydrolysate appears as an interesting candidate to prevent cognitive decline during aging.