Proportion Of Arachidonic Acid Research Articles

Janus kinase inhibitors modify the fatty acid profile of extracellular vesicles and modulate the immune response

BackgroundJanus kinase inhibitors (jakinibs) are immunomodulators used for treating malignancies, autoimmune diseases, and immunodeficiencies. However, they induce adverse effects such as thrombosis, lymphocytosis, and neutropenia that could be mediated by extracellular vesicles (EVs). These particles are cell membrane-derived structures that transport cellular and environmental molecules and participate in intercellular communication. Jakinibs can modify the content of EVs and enable them to modulate the activity of different components of the immune response. Objectiveto evaluate the interactions between immune system components of healthy individuals and EVs derived from monocytic and lymphoid lineage cells generated in the presence of baricitinib (BARI) and itacitinib (ITA) and their possible effects. MethodsEVs were isolated from monocytes (M) and lymphocytes (L) of healthy individuals, as well as from U937 (U) and Jurkat (J) cells exposed to non-cytotoxic concentrations of BARI, ITA, and dimethyl sulfoxide (DMSO; vehicle control). The binding to and engulfment of EVs by peripheral blood leukocytes of healthy individuals were analyzed by flow cytometry using CFSE-stained EVs and anti-CD45-PeCy7 mAb-labeled whole blood. The effect of EVs on respiratory burst, T-cell activation and proliferation, cytokine synthesis, and platelet aggregation was evaluated. Respiratory burst was assessed in PMA-stimulated neutrophils by the dihydrorhodamine (DHR) test and flow cytometry. T-cell activation and proliferation and cytokine production were assessed in CFSE-stained PBMC cultures stimulated with PHA; expression of the T-cell activation markers CD25 and CD69 and T-cell proliferation were analyzed by flow cytometry, and the cytokine levels were quantified in culture supernatants by Luminex assays. Platelet aggregation was analyzed in platelet-rich plasma (PRP) samples by light transmission aggregometry. The EVs’ fatty acid (FA) profile was analyzed using methyl ester derivatization followed by gas chromatography. ResultsITA exposure during the generation of EVs modified the size of the EVs released; however, treatment with DMSO and BARI did not alter the size of EVs generated from U937 and Jurkat cells. Circulating neutrophils, lymphocytes, and monocytes showed a 2-fold greater tendency to internalize ITA-U-EVs than their respective DMSO control. The neutrophil respiratory burst was attenuated in greater extent by M-EVs than by L-EVs. Autologous ITA-M-EVs reduced T-cell proliferation by decreasing IL-2 levels and CD25 expression independently of CD69. A higher accumulation of pro-inflammatory cytokines was observed in PHA-stimulated PBMC cultures exposed to M-EVs than to L-EVs; this difference may be related to the higher myristate content of M-EVs. Platelet aggregation increased in the presence of ITA-L/M-EVs by a mechanism presumably dependent on the high arachidonic acid content of the vesicles. ConclusionsCellular origin and jakinib exposure modify the FA profile of EVs, enabling them, in turn, to modulate neutrophil respiratory burst, T-cell proliferation, and platelet aggregation. The increased T-cell proliferation induced by BARI-L/M-EVs could explain the lymphocytosis observed in patients treated with BARI. The higher proportion of arachidonic acid in the FA content of ITA-L/M-EVs could be related to the thrombosis described in patients treated with ITA. EVs also induced a decrease in the respiratory burst of neutrophils.

Enriched PUFA environment of Leishmania infantum promastigotes promotes the accumulation of lipid mediators and favors parasite infectivity towards J774 murine macrophages.

Leishmania parasites are the causative agents of visceral or cutaneous leishmaniasis in humans and of canine leishmaniosis. The macrophage is the predilected host cell of Leishmania in which the promastigote stage is transformed into amastigote. We previously showed changes in the fatty acid composition (FA) of lipids in two strains of Leishmania donovani upon differentiation of promastigote to amastigote, including increased proportions of arachidonic acid (AA) and to a less extent of docosahexaenoic acid (DHA). Here, we carried out supplementation with AA or DHA on two Leishmania infantum strains, a visceral (MON-1) and a cutaneous (MON-24), to evaluate the role of these FA in parasite/macrophage interactions. The proportions of AA or DHA in total lipids were significantly increased in promastigotes cultured in AA- or DHA-supplemented media compared to controls. The content of FA-derived oxygenated metabolites was enhanced in supplemented strains, generating especially epoxyeicosatrienoic acids (11,12- and 14,15-EET) and hydroxyeicosatetraenoic acids (5- and 8- HETE) from AA, and hydroxydocosahexaenoic acids (14- and 17-HDoHE) from DHA. For both MON-1 and MON-24, AA-supplemented promastigotes showed higher infectivity towards J774 macrophages as evidenced by higher intracellular amastigote numbers. Higher infectivity was observed after DHA supplementation for MON-24 but not MON-1 strain. ROS production by macrophages increased upon parasite infection, but only minor change was observed between control and supplemented parasites. We propose that under high AA or DHA environment that is associated with AA or DHA enrichment of promastigote lipids, FA derivatives can accumulate in the parasite, thereby modulating parasite infectivity towards host macrophages.

Dietary plant oil supplemented with arachidonic acid and eicosapentaenoic acid affects the fatty acid composition and eicosanoid metabolism of Atlantic salmon (Salmo salar L.) during smoltification

This study sought to investigate whether a “natural diet” (mimicking the fatty acid composition of freshwater aquatic insects eaten by salmon parr) during the freshwater (FW) life stage of pre-smolt Atlantic salmon (Salmo salar L.) affected red blood cells and gill fatty acid composition as well as eicosanoid metabolism in gill during smolting at different temperatures. Before being transferred to seawater (SW), salmon parr were fed with a modified (MO) diet containing vegetable oils (rapeseed, palm, and linseed oils) supplemented with eicosapentaenoic acid (EPA) and arachidonic acid (ARA) to completely replace the fish oil (FO). Fatty acid composition in red blood cells and gill tissues was determined before SW transfer and six weeks after. Additionally, the expression of genes associated with eicosanoid metabolism and Na+/K+-ATPase (NKA) activity in salmon gill was examined at different temperatures before SW transfer and 24 h after. The results showed the changes in fatty acid composition, including sum monounsaturated fatty acids (MUFAs), docosahexaenoic acid (DHA), ARA, EPA, and sum n-6 polyunsaturated fatty acids (n-6 PUFA) in both red blood cells and gill tissues at the FW stage were consistent with the fatty acid profiles of the supplied MO and FO fish diets; however sum EPA and DHA composition exhibited opposite trends to those of the FO diet. The proportion of ARA, EPA, and n-6 PUFA increased, whereas sum MUFAs and DHA decreased in the red blood cells and gill tissues of MO-fed fish compared to those fed with the FO diet at FW stage. Additionally, 5-lipoxygenase-activating protein (Flap) expression was downregulated in MO-fed fish prior to SW transfer. During the process of SW transfer at different temperatures, the MO diet remarkably suppressed NKAα1a expression in MO-fed fish both at 12 and 16 °C. The MO diet also upregulated phospholipase A2 group IV (PLA2g4) expression in gills at 8, 12, and 16 °C, but suppressed phospholipase A2 group VI (PLA2g6) expression in gills at 12 °C compared to FO-fed fish at 12 °C and MO-fed fish at 8 °C. The MO diet also upregulated Cyclooxygenase 2 (Cox-2) expression at 8 °C compared to FO-fed fish and increased Arachidonate 5-lipoxygenase (5-Lox) expression in MO-fed fish at 16 °C compared to both FO-fed fish at 16 °C and MO-fed fish at 8 °C. Our study also determined that both SW transfer water temperatures and diets during the FW period jointly influenced the mRNA expression of PLA2g4, PLA2g6, and Lpl, whereas 5-Lox was more sensitive to dietary changes. In conclusion, the MO diet affected the fatty acid composition in gill and in red blood cells. When transferred to SW, dietary ARA supplementation could promote the bioavailability for eicosanoid synthesis in gill mainly via PLA2g4 activation, and potentially inhibit the stress and inflammatory response caused by different water temperatures through dietary EPA supplementation.

Erythrocyte fatty acid membrane composition in children on long-term parenteral nutrition enriched with ω-3 fatty acids

Composite lipid emulsions containing soybean oil (30%), medium-chain triglycerides (30%), olive oil (25%), and fish oil (15%) (SMOF) are now widely used. We aimed to evaluate the tolerance, the efficiency, and the erythrocyte fatty acid (FA) profile for children on long-term home parenteral nutrition (HPN) receiving a composite fish oil-based emulsion (FOLE). At baseline, children (n=46) with severe intestinal failure highly dependent on parenteral nutrition (PN) for ≥1 y were included in the study when they had received the composite FOLE for >6 mo. Out of this baseline group, only 25 children remained highly PN-dependent (SMOF1, n=25) and could be assessed a second time, 2.4 y later (SMOF2, n=25). An independent control group ("weaned off PN" group; n=24) included children who had been weaned off PN for >2 y (median: 4 y). RBC-FA composition was established by GC-MS. Growth parameters, plasma citrulline, conjugated bilirubin, FA profiles, and the Holman ratio (20:3ω-9/20:4ω-6) were compared between groups. No difference for growth parameters, citrulline, and bilirubin was observed between the SMOF groups after 2.4 y (0.2<P<0.8). The weaned-off group did not differ from the SMOF groups for growth parameters (0.2<P<0.4) but citrulline was higher (P<0.0001) and conjugated bilirubin lower (P<0.01). The composite FOLE induced higher proportions of EPA (20:5n-3) (8.4%±2.9%) and DHA (22:6n-3) (11.7%±2.2%) than what was observed in weaned-off children (0.8%±0.4% and 6.6%±2.3%, respectively) but lower proportions of arachidonic acid (20:4n-6). However, the Holman ratio did not vary between groups (P=0.9), whereas the PUFA concentrations varied widely. Long-term use of the composite FOLE was well tolerated in HPN-dependent children. The RBC-FA profile alterations were consistent with the ω-3 PUFA-enriched composition of this emulsion without evidence of essential FA deficiency.

Depletion of Omega-3 Fatty Acids in RBCs and Changes of Inflammation Markers in Patients With Morbid Obesity Undergoing Gastric Bypass

BackgroundBariatric surgery is considered the most effective treatment for severe obesity. Despite this wide success, bariatric surgery is associated with increased risks of nutritional deficiencies. ObjectivesTo examine whether Roux-en-Y-gastric bypass (RYGB) alters essential fatty acid (FA) status and inflammation markers. MethodsSubjects with obesity (n = 28; BMI > 40 kg/m2; mean age 48 years) were studied before and 1 year after RYGB. We collected blood samples before and 12 months after RYGB, and analyzed FA in RBCs and peripheral blood mononuclear cells (PBMC), and measured inflammation parameters in plasma. The proportion of total n-3 FAs was the primary outcome, while parameters related to other FAs and inflammation factors were the secondary parameters. In addition, PBMCs from 15 of the participants were cultured alone or with 100 and 200 μM DHA, and the production of IL-6, IL-1β, PGE2, and prostaglandin F2-alpha (PGF2α) was assayed after endotoxin (LPS) stimulation. ResultsRYGB induced a significant reduction of BMI (−30%) and improvement of insulin resistance (−49%). While the proportion of arachidonic acid was 15% higher after RYGB, the proportions of total and individual n-3 FAs were 50%–75% lower (P < 0.01). Consequently, the RBC omega-3 index and n-3:n-6 fatty acid ratio were 45% and 50% lower after surgery, respectively. In isolated PBMCs, LPS induced the production of IL-6, IL-1β, PGE2, and PGF2α in both pre- and post-RYGB cells, but the effects were 34%–65% higher (P < 0.05) after RYGB. This effect was abrogated by DHA supplementation. ConclusionsThis study presents evidence that RBC and PBMC n-3 FAs are severely reduced in patients with obesity after RYGB. DHA supplementation in PBMC moderates the production of inflammation markers, suggesting that n-3 FA supplementation would merit a trial in bariatric patients.

The FADS1 Genotype Modifies Metabolic Responses to the Linoleic Acid and Alpha-linolenic Acid Containing Plant Oils-Genotype Based Randomized Trial FADSDIET2.

The article investigates the FADS1 rs174550 genotype interaction with dietary intakes of high linoleic acid (LA) and high alpha-linolenic acid (ALA) on the response of fatty acid composition of plasma phospholipids (PLs), and of markers of low-grade inflammation and glucose-insulin homeostasis. One-hundred thirty homozygotes men for FADS1 rs174550 SNP (TT and CC genotypes) were randomized to an 8-week intervention with either LA- or ALA-enriched diet (13 E% PUFA). The source of LA and ALA are 30-50mL of sunflower oil (SFO, 62-63% LA) and Camelina sativa oil (CSO, 30- are randomized to an 35% ALA), respectively. In the SFO arm, there is a significant genotype x diet interaction for the proportion of arachidonic acid in plasma phospholipids (p < 0.001), disposition index (DI30 ) (p = 0.039), and for serum high-sensitive c-reactive protein (hs-CRP, p = 0.029) after excluding the participants with hs-CRP concentration of >10mg L-1 and users of statins or anti-inflammatory therapy. In the CSO arm, there are significant genotype x diet interactions for n-3 polyunsaturated fatty acids, but not for the clinical characteristics. The FADS1 genotype modifies the response to high PUFA diets, especially to high-LA diet. These findings suggest that approaches considering FADS variation may be useful in personalized dietary counseling.

Effects of dietary n‐3 long‐chain polyunsaturated fatty acids (n‐3 LC‐PUFAs) on growth performance, body composition and subcutaneous adipose tissue transcriptome analysis of juvenile yellow drum ( Nibea albiflora )

Yellow drum juveniles were fed with graded n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) diets (1.5–15.9 g/kg) for ten weeks. Fish growth performance was firstly promoted then inhibited by increased n-3 LC-PUFAs inclusion. The optimum n-3 LC-PUFAs were 9.0 g kg−1 and 9.5 g kg−1, referring to the weight gain rate and feed efficiency ratio, respectively. The increased n-3 LC-PUFAs inclusion significantly decreased ash and moisture content but increased crude lipid content (p < .05). No significant alteration in fish protein content was observed among groups. Significantly higher saturated fatty acids proportion but the lower arachidonic acid proportion was observed in the subcutaneous adipose tissue (SCAT) of fish fed the diet with optimum n-3 LC-PUFAs group (9.8 g kg−1), compared with those of the control group (1.5 g kg−1) (p < .05). Transcriptome analysis found differently expressed genes (DEGs) were mostly enriched in the peroxisome and fatty acid biosynthesis pathways. Besides, the expression of an immune-related gene, Interleukin-17D was observed to significantly changed (p < .05). Therefore, 9.0–9.5 g kg−1 n-3 LC-PUFAs could be regarded as optimum for the yellow drum. Dietary n-3 LC-PUFAs affected the SCAT some metabolism and immunity genes expression.

Lipidome Remodeling and Autophagic Respose in the Arachidonic-Acid-Rich Microalga Lobosphaera incisa Under Nitrogen and Phosphorous Deprivation

The green microalga Lobosphaera incisa accumulates triacylglycerols (TAGs) with exceptionally high levels of long-chain polyunsaturated fatty acid (LC-PUFA) arachidonic acid (ARA) under nitrogen (N) deprivation. Phosphorous (P) deprivation induces milder changes in fatty acid composition, cell ultrastructure, and growth performance. We hypothesized that the resource-demanding biosynthesis and sequestration of ARA-rich TAG in lipid droplets (LDs) are associated with the enhancement of catabolic processes, including membrane lipid turnover and autophagic activity. Although this work focuses mainly on N deprivation, a comparative analysis of N and P deprivation responses is included. The results of lipidomic profiling showed a differential impact of N and P deprivation on the reorganization of glycerolipids. The formation of TAG under N deprivation was associated with the enhanced breakdown of chloroplast glycerolipids and the formation of lyso-lipids. N-deprived cells displayed a profound reorganization of cell ultrastructure, including internalization of cellular material into autophagic vacuoles, concomitant with the formation of LDs, while P-deprived cells showed better cellular ultrastructural integrity. The expression of the hallmark autophagy protein ATG8 and the major lipid droplet protein (MLDP) genes were coordinately upregulated, but to different extents under either N or P deprivation. The expression of the Δ5-desaturase gene, involved in the final step of ARA biosynthesis, was coordinated with ATG8 and MLDP, exclusively under N deprivation. Concanamycin A, the inhibitor of vacuolar proteolysis and autophagic flux, suppressed growth and enhanced levels of ATG8 and TAG in N-replete cells. The proportions of ARA in TAG decreased with a concomitant increase in oleic acid under both N-replete and N-deprived conditions. The photosynthetic apparatus’s recovery from N deprivation was impaired in the presence of the inhibitor, along with the delayed LD degradation. The GFP-ATG8 processing assay showed the release of free GFP in N-replete and N-deprived cells, supporting the existence of autophagic flux. This study provides the first insight into the homeostatic role of autophagy in L. incisa and points to a possible metabolic link between autophagy and ARA-rich TAG biosynthesis.

Meat Quality and Fatty Acid Profiles of Chinese Ningxiang Pigs Following Supplementation with N-Carbamylglutamate.

Simple SummaryN-carbamylglutamate (NCG) has been demonstrated to promote the synthesis of endogenous arginine and improve reproductive performance. In the present study, we found that dietary NCG supplementation improved meat quality of a Chinese fat-type pig by increasing muscle tenderness and Phe concentration, and optimizing fatty acid profiles in different tissues. These results provided scientific evidence for the application of NCG as a feed additive in finishing pigs.The present study evaluated the effects of dietary N-carbamylglutamate (NCG) on carcass traits, meat quality, and fatty acid profiles in the longissimus dorsi muscle and adipose tissues of Chinese Ningxiang pigs. A total of 36 castrated female pigs with a similar initial weight (43.21 ± 0.57 kg) were randomly assigned to two treatments (with six pens per treatment and three pigs per pen) and fed either a basal diet or a basal diet supplemented with 0.08% NCG for 56 days. Results showed that dietary NCG reduced shear force (p = 0.004) and increased drip loss (p = 0.044) in longissimus dorsi muscle of Ningxiang pigs. Moreover, increased levels of oleic acid (C18:1n9c) (p = 0.009), paullinic acid (C20:1) (p = 0.004), and α-linolenic acid (C18:3n3) (p < 0.001), while significant reduction in the proportions of arachidonic acid (C20:4n6) (p < 0.001) and polyunsaturated fatty acid (PUFA) (p = 0.017) were observed in the longissimus dorsi muscle of pigs fed NCG when compared with those fed the control diet. As for adipose tissues, the C20:1 (p = 0.045) proportion in dorsal subcutaneous adipose (DSA), as well as the stearic acid (C18:0) (p = 0.018) level in perirenal adipose (PA) were decreased when pigs were fed the NCG diet compared with those of the control diet. In contrast, the margaric acid (C17:0) (p = 0.043) proportion in PA were increased. Moreover, the NCG diet produced PA with a greater proportion of total PUFAs (p = 0.001) (particularly linoleic acid (C18:2n6c) (p = 0.001)) compared with those produced by the control diet. These findings suggest that dietary NCG has beneficial effects by decreasing the shear force and improving the healthfulness of fatty acid profiles, providing a novel strategy for enhancing meat quality of pigs.

Human milk fatty acid composition is associated with dietary, genetic, sociodemographic, and environmental factors in the CHILD Cohort Study

Fatty acids are a vital component of human milk. They influence infant neurodevelopment and immune function, and they provide ∼50% of milk's energy content. The objectives of this study were to characterize the composition of human milk fatty acids in a large Canadian birth cohort and identify factors influencing their variability. In a subset of the CHILD cohort (n=1094), we analyzed milk fatty acids at 3-4 mo postpartum using GLC. Individual and total SFAs, MUFAs, and n-3 and n-6 PUFAs were analyzed using SD scores and principal component analysis (PCA). Maternal diet, sociodemographic, health, and environmental factors were self-reported. Single-nucleotide polymorphisms were assessed in the fatty acid desaturase 1 (FADS1-rs174556) and 2 (FADS2-rs174575) genes. Fatty acid profiles were variable, with individual fatty acid proportions varying from 2- to >30-fold between women. Using PCA, we identified 4 milk fatty acid patterns: "MUFA and low SFA," "high n-6 PUFA," "high n-3 PUFA," and "high medium-chain fatty acids." In multivariable-adjusted analyses, fish oil supplementation and fatty cold water fish intake were positively associated with DHA and the "high n-3 PUFA" pattern. Mothers carrying the minor allele of FADS1-rs174556 had lower proportions of arachidonic acid (ARA; 20:4n-6). Independent of selected dietary variables and genetic variants, Asian ethnicity was associated with higher linoleic acid (18:2n-6) and total n-3 PUFAs. Ethnic differences in ARA were explained by FADS1 genotype. Maternal obesity was independently associated with higher total SFAs, the "high medium-chain fatty acid" pattern, and lower total MUFAs. Lactation stage, season, study site, and maternal education were also independently associated with some milk fatty acids. No associations were observed for maternal age, parity, delivery mode, or infant sex. This study provides unique insights about the "normal" variation in the composition of human milk fatty acids and the contributing dietary, genetic, sociodemographic, health, and environmental factors. Further research is required to assess implications for infant health.

Contrasting effects of membrane enrichment with polyunsaturated fatty acids on phospholipid composition and cholesterol efflux from cholesterol-loaded J774 mouse or primary human macrophages

A high consumption of polyunsaturated fatty acids (PUFAs), particularly n-3 PUFAs, is atheroprotective. PUFAs incorporation into membrane phospholipids alters the functionality of membrane proteins. We studied the consequences of the in vitro supplementation of several PUFAs on the FA profiles and on ABCA1-dependent cholesterol efflux capacities from cholesterol-loaded macrophages. Arachidonic acid (AA, C20:4 n-6) and, to a lesser extent, eicosapentaenoic acid (EPA, C20:5 n-3), dose-dependently impaired cholesterol efflux from cholesterol-loaded J774 mouse macrophages without alterations in ABCA1 expression, whereas docosahexaenoic acid (DHA, C22:6 n-3) had no impact. AA cells exhibited higher proportions of arachidonic acid and adrenic acid (C22:4 n-6), its elongation product. EPA cells exhibited slightly higher proportions of EPA associated with much higher proportions of docosapentaenoic acid (C22:5 n-3), its elongation product and with lower proportions of AA. Conversely, both EPA and DHA and, to a lesser extent, AA decreased cholesterol efflux from cholesterol-loaded primary human macrophages (HMDM). The differences observed in FA profiles after PUFA supplementations were different from those observed for the J774 cells. In conclusion, we are the first to report that AA and EPA, but not DHA, have deleterious effects on the cardioprotective ABCA1 cholesterol efflux pathway from J774 foam cells. Moreover, the membrane incorporation of PUFAs does not have the same impact on cholesterol efflux from murine (J774) or human (HMDM) cholesterol-loaded macrophages. This finding emphasizes the key role of the cellular model in cholesterol efflux studies and may partly explain the heterogeneous literature data on the impact of PUFAs on cholesterol efflux.

Reviews and syntheses: Insights into deep-sea food webs and global environmental gradients revealed by stable isotope (&amp;lt;i&amp;gt;δ&amp;lt;/i&amp;gt;&amp;lt;sup&amp;gt;15&amp;lt;/sup&amp;gt;N, &amp;lt;i&amp;gt;δ&amp;lt;/i&amp;gt;&amp;lt;sup&amp;gt;13&amp;lt;/sup&amp;gt;C) and fatty acid trophic biomarkers

Abstract. Biochemical markers developed initially for food-web studies of terrestrial and shallow-water environments have only recently been applied to deep-sea ecosystems (i.e., in the early 2000s). For the first time since their implementation, this review took a close look at the existing literature in the field of deep-sea trophic ecology to synthesize current knowledge. Furthermore, it provided an opportunity for a preliminary analysis of global geographic (i.e., latitudinal, along a depth gradient) trends in the isotopic (δ15N, δ13C) and fatty acid composition of deep-sea macro- and megafauna from heterotrophic systems. Results revealed significant relationships along the latitudinal and bathymetric gradients. Deep-sea animals sampled at temperate and polar latitudes displayed lower isotopic ratios and greater proportions of essential ω3 long-chain polyunsaturated fatty acids (LC-PUFAs) than did tropical counterparts. Furthermore, δ15N and δ13C ratios as well as proportions of arachidonic acid increased with increasing depth. Since similar latitudinal trends in the isotopic and fatty acid composition were found in surface water phytoplankton and particulate organic matter, these results highlight the link across latitudes between surface primary production and deep-water communities. Because global climate change may affect quantity and quality (e.g., levels of essential ω3 PUFAs) of surface primary productivity, and by extension those of its downward flux, the dietary intake of deep-sea organisms may likely be altered. In addition, because essential ω3 PUFAs play a major role in the response to temperature variations, climate change may interfere with the ability of deep-sea species to cope with potential temperature shifts. Importantly, methodological disparities were highlighted that prevented in-depth analyses, indicating that further studies should be conducted using standardized methods in order to generate more reliable global predictions.

Fatty acids, sterols, phenolic compounds, and carotenoid changes in response to dietary inclusion of Ulva clathrata in shrimp Litopenaeus vannamei broodstock

Changes in lipid reserves as a result of supplementing 3.4% Ulva clathrata meal in the diet (based on dry weight of all ingredienta) for Litopenaeus vannamei broodstock were evaluated in a commercial larval laboratory. The profile of fatty acids, sterols, carotenoids, and phenolic compounds in the gonad, hepatopancreas, and muscle of females with unilateral ablation was analyzed. Shrimp fed the Ulva supplemented diet had significantly higher proportions of arachidonic acid (20:4n-6) in the acylglycerides of mature gonads (84% increase) compared with mature controls. In the phospholipids of mature gonads, there was a 30% increase of 18:3n-3, 13% increase of 20:4n-6, and 10% of docosahexaenoic acid (22:6n-3) in Ulva-fed shrimp compared with controls. 22:6n-3 also increased 51% in the lipid reserves of hepatopancreas of Ulva-fed shrimp compared with controls. Carotenoids increased by 43% in the gonads and fivefold in the hepatopancreas of mature females fed Ulva. The proportion of fucosterol and isofucosterol went from undetectable in controls to 0.3 and 0.2%, respectively, in shrimp fed the algae. No significant differences were found in muscle. Phenolic compounds in the gonad were higher in mature gonads compared with immature, but no significant differences were found in relation to Ulva consumption. Carotenoids and phenolic compounds present in Ulva might be acting as antioxidants of highly unsaturated fatty acids (HUFAs), increasing the proportion of 20:4n-6 and 22:6n-3, but other mechanisms associated to these compounds and to fucosterol can be synchronizing oocyte maturation and increasing transport of HUFA during vitellogenesis, and together, they are further impacting the reproductive performance of shrimp.

Human Milk Fatty Acid Composition Is Associated with Dietary, Genetic, Sociodemographic and Environmental Factors in the CHILD Cohort (P08-114-19)

ObjectivesHuman milk fatty acids impact infant growth and development, and their composition is highly variable. We aimed to characterize milk fatty acid composition in a large pregnancy cohort and identify factors that influence their variability. MethodsAmong 1094 mothers from the CHILD cohort, we analyzed milk collected at 3–4 months postpartum. Fatty acids were measured by high-resolution capillary gas-liquid chromatography. Individual fatty acids, total saturated (SFA), monounsaturated (MUFA), n3 and n6-polyunsaturated fatty acids (n3-PUFA and n6-PUFA) were analyzed as standard deviation scores and using principal components analysis (PCA). Maternal diet, sociodemographic, health and environmental factors were self-reported. Single-nucleotide polymorphisms were assessed in genes encoding fatty acid desaturase 1 (FADS1 rs174556) and FADS2 (rs174575). ResultsUsing PCA, we identified four milk fatty acid patterns: ‘MUFA and low SFA’, ‘high n6-PUFA’, ‘high n3-PUFA’ and ‘high medium-chain fatty acids’. In multivariable-adjusted analyses, fish oil supplementation and fatty cold water fish intake were positively associated with docosohexanoic acid and the “high-n3-PUFA” pattern. Mothers carrying the minor allele of FADS1 rs174556 (C > T) had lower proportions of arachidonic acid (ARA). Independent of dietary and genetic factors, Asian ethnicity was associated with higher linoleic acid and total n3-PUFA. Ethnic differences in ARA were explained by the FADS1 genotype. Maternal obesity was independently associated with higher total SFA and ‘high medium-chain fatty acid’ pattern, and lower total MUFA. Lactation stage, season, study site, and maternal education were also independently associated with some milk fatty acids. No associations were observed for maternal age, parity, smoking, delivery mode, or infant sex. ConclusionsThese results suggest that a combination of diet, genetics, sociodemographic, health and environmental factors influence human milk fatty acid patterns. Together, these factors explained about 25% of the variation observed in n3-PUFAs and n6-PUFAs and about 10% of the variation observed in SFAs and MUFAs. Implications of these findings for maternal and infant health requires further research. Funding SourcesManitoba Medical Service Foundation; Children’s Hospital Research Institute of Manitoba; CIHR; AllerGen.

Exposure to a Farm Environment During Pregnancy Increases the Proportion of Arachidonic Acid in the Cord Sera of Offspring.

Growing up in a farm environment is protective against allergy development. Various explanations have been put forward to explain this association. Fatty acids are regulators of immune function and the composition of fatty acids in the circulation system may affect immune development. Here, we investigate whether the fatty acid composition of cord serum differs for infants born to Farm (n = 26) or non-Farm mothers (n = 29) in the FARMFLORA birth-cohort. For comparison, the levels of fatty acids in the maternal diet, serum and breast milk around 1 month post-partum were recorded. The fatty acids in the cord sera from infants born to Farm mothers had higher proportions of arachidonic acid (20:4 n-6) and adrenic acid (22:4 n-6) than those from infants born to non-Farm mothers. No differences were found for either arachidonic acid or adrenic acid in the diet, samples of the serum, or breast milk from Farm and non-Farm mothers obtained around 1 month post-partum. The arachidonic and adrenic acid levels in the cord blood were unrelated to allergy outcome for the infants. The results suggest that a farm environment may be associated with the fatty acid composition to which the fetus is exposed during pregnancy.

Inflammatory response to dietary linoleic acid depends on FADS1 genotype

The health benefits of substituting dietary polyunsaturated fatty acids (PUFAs) for saturated fatty acids are well known. However, limited information exists on how the response to dietary intake of linoleic acid (LA; 18:2n-6) is modified by polymorphisms in the fatty acid desaturase (FADS) gene cluster. The aim of the current study was to test the hypothesis that the FADS1 rs174550 genotype modifies the effect of dietary LA intake on the fatty acid composition of plasma lipids, fasting glucose, and high-sensitivity C-reactive protein (hsCRP). Associations were investigated between genotype, plasma PUFAs, fasting glucose, and hsCRP concentrations in the cross-sectional, population-based Metabolic Syndrome in Men cohort (n=1337). In addition, 62 healthy men from the cohort who were homozygotes for the TT or CC genotype of the FADS1 rs174550 were recruited to a 4-wk intervention (FADSDIET) with an LA-enriched diet. The fatty acid composition of plasma PUFAs and concentrations of plasma fasting glucose, serum hsCRP, and plasma lipid mediators (eicosanoids and related analogs) were measured at the beginning and end of the 4-wk intervention period. In the FADSDIET trial, the plasma LA proportion increased in both genotype groups in response to an LA-enriched diet. Responses in concentrations of serum hsCRP and plasma fasting glucose and the proportion of arachidonic acid (20:4n-6) in plasma phospholipids and cholesteryl esters differed between genotype groups (interaction of diet × genotype, P<0.05). In TT homozygous subjects, plasma eicosanoid concentrations correlated with the arachidonic acid proportion in plasma and with hsCRP (r=0.4-0.7, P<0.05), whereas in the CC genotype there were no correlations. Our findings show that the FADS1 genotype modifies metabolic responses to dietary LA. The emerging concept that personalized dietary counseling should be modified by the FADS1 genotype needs to be tested in larger randomized trials. The study was registered at clinicaltrials.gov as NCT02543216.

The type 2 acyl-CoA:diacylglycerol acyltransferase family of the oleaginous microalga Lobosphaera incisa

BackgroundOleaginous microalgae are promising sources of energy-rich triacylglycerols (TAGs) for direct use for food, feed and industrial applications. Lobosphaera incisa is a fresh water unicellular alga, which in response to nutrient stress accumulates a high amount of TAGs with a high proportion of arachidonic acid (ARA). The final committed step of de novo TAG biosynthesis is catalyzed by acyl-CoA:diacylglycerol acyltransferases (DGATs), which add a fatty acid (FA) to the final sn-3 position of diacylglycerol (DAG).ResultsGenome analysis revealed the presence of five putative DGAT isoforms in L. incisa, including one DGAT of type 1, three DGATs of type 2 and a single isoform of a type 3 DGAT. For LiDGAT1, LiDGAT2.1, LiDGAT2.2 and LiDGAT2.3 enzyme activity was confirmed by expressing them in the TAG-deficient yeast strain H1246. Feeding experiments of yeast transformants with fatty acids suggest a broad substrate specificity spectrum for LiDGAT1. A significant TAG production in response to exogenous ARA was found for LiDGAT2.2. Cellular localization of the four type 1 and type 2 DGATs expressed in yeast revealed that they all localize to distinct ER domains. A prominent association of LiDGAT1 with ER domains in close proximity to forming lipid droplets (LDs) was also observed.ConclusionsThe data revealed a distinct molecular, functional and cellular nature of type 1 and type 2 DGATs from L. incisa, with LiDGAT1 being a major contributor to the TAG pool. LiDGATs of type 2 might be in turn involved in the incorporation of unusual fatty acids into TAG and thus regulate the composition of TAG. This report provides a valuable resource for the further research of microalgae DGATs oriented towards production of fresh-water strains with higher oil content of valuable composition, not only for oil industry but also for human and animal nutrition.

Effects of altering the ratio of dietary n-6 to n-3 fatty acids on spontaneous luteolysis in lactating dairy cows

Objectives were to evaluate the effects of altering the dietary ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids on the profile of fatty acids and expression of genes related to the prostaglandin biosynthesis on endometrial tissue, uterine secretion of PGF2α, and timing of spontaneous luteolysis in dairy cows. Multiparous lactating Holstein cows (n = 45) were blocked based on milk yield and, within each block, assigned randomly to 1 of 3 dietary treatments at 14 d postpartum for 90 d. Diets were supplemented with a mixture of Ca salts of fish, safflower, and palm oils to create 3 different ratios of n-6 to n-3 fatty acids, namely R4, R5, and R6, which resulted in 3.9, 4.9, and 5.9 parts of n-6 to 1 part of n-3 fatty acids, respectively. Blood was sampled every 2 h from d 16 to 23 of the estrous cycle and assayed for concentrations of progesterone and the PGF2α metabolite 13,14-dihydro-15-keto-PGF2α (PGFM). In a subsequent estrous cycle, endometrial tissue was collected for biopsy on d 8 and endometrial fatty acids profile and gene expression were quantified. The proportion of arachidonic acid of the endometrial fatty acids increased as the dietary ratio n-6 to n-3 fatty acids increased (R4 = 9.05, R5 = 11.64, and R6 = 13.41%). On the other hand, proportions of eicosapentaenoic (R4 = 2.85, R5 = 2.14, and R6 = 2.02%) and docosahexaenoic (R4 = 3.30, R5 = 1.57, and R6 = 1.08%) decreased as the ratio of n-6 to n-3 fatty acids in the diet increased. Increasing the ratio of dietary n-6 to n-3 fatty acids increased mRNA expression of estrogen receptor 1, oxytocin receptor, cyclooxygenase 2, prostaglandin E and F synthases, and steroidogenic acute regulatory protein in endometrium, but decreased expression of peroxisome proliferator-activated receptor gamma and insulin-like growth factor-1. The changes in endometrium gene expression caused by dietary treatments were associated with changes in the ratio of n-6 to n-3 fatty acids in the endometrium. As the ratio increased from R4 to R6, the number of PGFM pulses (R4 = 5.6, R5 = 4.3, and R6 = 3.8 ± 0.6 pulses; least squares means ± standard error of the means) decreased, but the amplitude of the greatest PGFM pulse increased (R4 = 226, R5 = 267, and R6 = 369 ± 38 pg/mL). Luteolysis by d 23 of the estrous cycle was observed in 79.6% of the cows (R4 = 11/14; R5 = 13/15; and R6 = 11/15) and day of spontaneous luteolysis did not differ among treatments (R4 = 20.8; R5 = 21.1; and R6 = 21.0 ± 0.4). Three pulses of PGFM was the best predictor of luteolysis in dairy cows. Collectively, supplying the same quantity of fatty acids in the diet of lactating dairy cows, but altering the ratio of n-6 to n-3 fatty acids, influenced the endometrial fatty acids profile and gene expression and altered the pattern of prostaglandin synthesis; however, the changes were not sufficient to alter the length of the estrous cycle.

Joint effects of fatty acid desaturase 1 polymorphisms and dietary polyunsaturated fatty acid intake on circulating fatty acid proportions

Polyunsaturated fatty acids (PUFAs) are associated with a lower risk of multiple diseases. Fatty acid desaturase 1 gene (FADS1) polymorphisms and dietary PUFA intake are both established determinants of circulating PUFA proportions. We explored the joint effects of FADS1 polymorphisms and dietary PUFA intake on circulating PUFA proportions. We studied 2288 participants from a nested case-control study of coronary artery disease among participants who provided blood samples in the Nurses' Health Study and the Health Professionals Follow-Up Study. Dietary PUFA intake was obtained from semiquantitative food-frequency questionnaires. FADS1 rs174546 was genotyped by using the Affymetrix 6.0 platform, and circulating PUFA proportions were measured with gas-liquid chromatography. Linear regression models were used to examine the associations between rs174546 and circulating proportions of each fatty acid. Gene-diet interactions were tested by including a cross-product term of dietary intake of each PUFA by rs174546 genotype in the linear regression models. After adjustment for sex and ancestry, each copy of the C allele of rs174546 was associated with higher circulating proportions of arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and lower proportions of linoleic acid and α-linolenic acid. The magnitude of positive association between higher consumption of dietary EPA or DHA and circulating proportions of EPA increased with each copy of the rs174546_T allele (P-interaction=0.01 and 0.007, respectively). Each 1-SD increment in EPA intake was associated with an average 3.7% increase in circulating EPA proportions among participants with the rs174546_CC genotype and an average 7.8% increase among participants with the TT genotype. Carriers of the T allele at FADS1 rs174546 may need higher doses of dietary EPA and DHA to achieve the same circulating proportions of EPA as carriers of the C allele. The implications of these findings on disease risk and dietary guidelines require further study.

The red blood cell proportion of arachidonic acid relates to shorter leukocyte telomeres in Mediterranean elders: A secondary analysis of a randomized controlled trial

Shortening of leukocyte telomere length (LTL) is a biomarker of aging. Epidemiologic studies of LTL in relation to dietary fatty acids have reported conflicting results. The red blood cell (RBC) fatty acid status is a valid objective biomarker of long-term dietary intake of C18:2n-6, C18:3n-3 and long-chain n-3 polyunsaturated fatty acids (C20:5n-3 and C22:6n-3). In healthy older individuals, we investigated whether LTL relates to the RBC proportions of the main dietary polyunsaturated fatty acids (PUFA), and to the RBC proportion of arachidonic acid (C20:4n-6), a fatty acid that can generate pro-inflammatory lipid mediators once released from cell membranes. Cross-sectional study in 344 subjects (mean age 68.8y, 68.6% women) who participated in a randomized controlled trial testing whether a diet enriched in walnuts can delay the onset of age-related diseases (https://clinicaltrials.gov/ct2/show/NCT01634841). At baseline, we assessed LTL by high-throughput quantitative fluorescence and determined fatty acids in RBCs by gas chromatography. In multivariate models adjusted for age and gender, the RBC proportions of dietary PUFA were unrelated to LTL. In contrast, the RBC proportion of arachidonic acid inversely related to LTL (regression coefficient [95% confidence interval],-0.10 (-0.19 to-0.01), P=0.023). An increasing proportion of C20:4n-6 in RBCs is associated with shorter telomeres. Further research is needed to investigate the role of this fatty acid and its derived lipid mediators in the aging process.