Prostaglandins, Leukotrienes and Essential Fatty Acids

Variants in the CYSLTR2 are associated with asthma, atopy markers and helminths infections in the Brazilian population Publication date: June 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 145 Author(s): Talita dos S. Jesus, Ryan dos S. Costa, Neuza Maria Alcântara-Neves, Maurício L. Barreto, Camila Alexandrina Figueiredo Abstract Background Asthma is a chronic disease of the airways and its most common phenotype is characterized by a T2 type response with IgE production and inflammatory mediators in response to common allergens. Cysteinyl leukotrienes (CysLTs), LTC4, LTD4 and LTE4, are mediators known to possess important proinflammatory action. CysLTs can bind to the Cysteinyl leukotriene receptor type 2 (CysLTR2) and activate an inflammatory. Polymorphisms in CysLTR2 have been associated with asthma and atopy, although the mechanism is not clear. Objective To evaluate the association between genetic polymorphisms in CYSLTR2 with asthma phenotypes, atopy markers and helminth infection. Methods Genotyping was performed using a panel Illumina and carried out in 1245 participants of SCAALA program (Social Change, Asthma, Allergy in Latin American). Logistic regressions for asthma, helminth infections (Trichuris trichiura and Ascaris lumbricoides) and allergy markers (skin tests and IgE production) were performed using PLINK 1.9 software adjusted for sex, age, helminth infection and ancestry markers. Results The G allele of rs1323556 was negatively associated with asthma in the additive model (OR 0.74, 95% CI 0.59–0.93) and in the dominant model (OR 0.71, 95% CI 0.53–0.74). The G allele of rs1575464 was also negatively associated with asthma in two genetic models, additive (OR 0.77, 95% CI 0.62–0.96) and dominant (OR 0.73, 95% CI 0.55–0.97). The G allele of rs61735175 was positively associated with asthma severity in the additive model (OR 1.72, 95% CI 1.07–2.77) and in the dominant model (OR 1.77, 95% CI 1.09–2.85). Five SNVs were associated with atopy markers and four SNVs were associated with helminth infections. Conclusion Polymorphisms in the CYSLTR2 gene are associated with asthma, atopy markers and helminth infection in Brazilian individuals, which may lead to protection or risk for such conditions, however, more studies are needed to evaluate the functional of this variants here in described.

Quantitating fatty acids in dried blood spots on a common collection card versus a novel wicking sampling device Publication date: June 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 145 Author(s): Jan Gunash, Juan J. Aristizabal-Henao, Ken D. Stark Abstract Blood biomarkers of n − 3 polyunsaturated fatty acids can serve as indicators of dietary intake and benefits and/or disease risk. The use of dried blood spots for fatty acid analyses is increasing but most of the reported data is qualitative (relative percentages of total fatty acids). The ability to quantitate concentrations of fatty acids on a common blood spot collection card and a novel wicking device designed to collect 10 µL of blood was compared with a wet blood sample in ten young adult participants. Prior to this comparison, the collection materials were screened for contaminants by gas chromatography with flame ionization and liquid chromatography/tandem mass spectrometry, and the blood volume and blood spot area relationship of the collection card was confirmed using technical replicates. Palmitate and stearate were detected as free fatty acids on both collection materials and as lysophosphatidylcholines on the wicking device. The low amounts (<1.0 µg) did not affect the quantitation of these fatty acids in either material. The relationship between blood volume and blood spot area was linear (r = 0.99, p < 0.001) and it was determined that a 6 mm hole punch contained 9.6 µL of blood. When compared with wet blood, the fatty acid determinations from the dried blood spots were largely similar although there were some minor differences in low abundant fatty acids. Quantitative fatty acid determinations of dried blood spots are possible and should be reported along with relative percentage data to improve interpretation in the future.

Physical fitness is associated with prostaglandin F2α isomers during pregnancy Publication date: June 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 145 Author(s): Jean-François Bilodeau, Michèle Bisson, Jessica Larose, Etienne Pronovost, Mélanie Brien, Karine Greffard, Isabelle Marc Abstract Introduction Pregnancy and physical activity are associated with oxidative stress and immune changes. We hypothesized that pregnant women physically more active in early pregnancy will display a better oxidative stress management and inflammatory response later in pregnancy compared with less active pregnant women. Material and methods Maternal physical activity using accelerometry monitors for 1 week and cardiorespiratory fitness (VO2 at anaerobic threshold) were assessed at 14–18 weeks in 58 pregnant women. Plasma and erythrocytes membrane samples were obtained from maternal blood samples at 14–18 and 34–37 weeks of pregnancy. Pro-inflammatory prostaglandin (PG) F2α and oxidative stress-derived F2-isoprostanes were measured by high-performance liquid chromatography coupled to tandem mass spectrometry. Results Higher physical activity levels at 14–18 weeks measured by mean counts per minute, >30 min/d of moderate to vigorous activity or >6500 steps/d at 14–18 weeks of pregnancy were associated with lower levels of total plasmatic PGF2α later in pregnancy. Concentrations of 5 F2-isomers in erythrocyte membranes in late pregnancy were significantly higher in the third (17.5–19.5 mL kg−1 min−1) and/or fourth (19.6–27.7 mL kg−1 min−1) quartiles of cardio-respiratory fitness compared to the first quartile (13.9–15.9 mL kg−1 min−1). Conclusions Overall, higher cardio-respiratory fitness in early pregnancy is associated with enhanced erythrocyte membranes oxidation at 34–37 weeks reflecting a higher oxygen transfer capacity. Also, the most active women experienced lower circulating levels of pro-inflammatory PGF2α in plasma at 34–37 weeks, a marker associated with adverse antenatal inflammation-associated conditions. These results support the practice of physical activity by pregnant women.

Relationship of Omega-3 Fatty Acids DHA and EPA with the Inflammatory Biomarker hs-CRP in Children with Sickle Cell Anemia Publication date: Available online 10 May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): B N Yamaja Setty, Suhita Gayen Betal, Robin E Miller, Dawn S Brown, Maureen Meier, Michele Cahill, Norma B Lerner, Nataly Apollonsky, Marie J Stuart Abstract Background Inflammation and vaso-occlusion play key roles in Sickle Cell Disease (SCD) pathophysiology. Lipoxygenase products of the omega-3 fatty acids (O3FAs), docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, are potent anti-inflammatory mediators modulating pain. O3FAs decrease episodes of vaso-occlusion in SCD. Methods We assessed erythrocyte fatty acid composition in two major cell membrane phospholipids, phosphatidylcholine and phosphatidylethanolamine, in children with SCD HbSS-disease (n=38) and age/race-matched HbAA-controls (n=18). Ratio of pro-inflammatory arachidonic acid (AA) to anti-inflammatory DHA and EPA (FA-Ratio), and its relationship to hs-CRP were evaluated. Results FA-Ratios were increased in both phosphatidylcholine and phosphatidylethanolamine in HbSS compared to controls. Correlations were noted in HbSS subjects between hs-CRP and FA-Ratios (p=0.011). FA-Ratios increased with age (p=0.0007) due to an increase in pro-inflammatory AA with a concomitant decrease in anti-inflammatory DHA. Conclusions Findings demonstrate relative deficiencies in HbSS of the anti-inflammatory precursor fatty acids DHA and EPA, which correlates positively with hs-CRP.

Gestational age and maternal status of DHA and other polyunsaturated fatty acids in pregnancy: A systematic review Publication date: May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 144 Author(s): Nina A. Wilson, Evangeline Mantzioris, Philippa T. Middleton, Beverly S. Muhlhausler Abstract Introduction Maternal diet is important in determining omega-3 DHA status however there is limited knowledge of other factors influencing maternal omega-3 concentrations during pregnancy. The primary objective of this systematic review and meta-analysis was to evaluate whether maternal DHA status changed across gestation. Changes in levels of other key polyunsaturated fatty acids were also investigated. Materials and methods The Medline, Embase, Amed, and CINAHL databases were searched. Included studies reported measures of maternal omega-3 status in at least two pregnancy trimesters. Results Thirteen studies were included in the final analyses. Absolute omega-3 DHA concentrations increased across gestation, but decreased as a proportion of total lipids. Discussion Our findings are consistent with previous observations of increases in lipid mobilisation, coupled with preferential transfer of DHA to the fetus, with advancing gestation. However the number of eligible studies was small and further investigations are required.

Associations of medium and long chain omega-3 polyunsaturated fatty acids with blood pressure in Hispanic and non-Hispanic smokers and nonsmokers Publication date: May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 144 Author(s): Kayla R. Zehr, Allison Segovia, Meera Shah, Mary T. Walsh-Wilcox, Barbara H. Brumbach, Joe R. Anderson, Mary K. Walker Summary Epidemiology studies and clinical trials have shown that omega-3 polyunsaturated fatty acids (n-3 PUFAs) are inversely associated with blood pressure. We sought to determine the influence of cigarette smoking and Hispanic ethnicity on this association. Age- and sex-matched smokers and nonsmokers (n = 98) 19–50 years old lacking cardiovascular disease were recruited. Systolic and diastolic blood pressure (SBP, DBP), heart rate, HbA1c, lipids, BMI, and RBC fatty acids were measured. The omega-3 index (percent eicosapentaenoic and docosahexaenoic acid, EPA+DHA, in RBCs) was significantly lower in smokers (Smokers: 3.19 ± 0.86%; Nonsmokers, 3.88 ± 1.05%, p = 0.001) and Hispanics (Hispanic 3.32 ± 0.93%; Non-Hispanic, 3.82 ± 1.03%, p = 0.006). DHA exhibited a significant inverse association with BP in both smokers and nonsmokers, while alpha-linolenic acid (ALA) exhibited a significant positive association with BP only in smokers. Multiple regression analyses showed that BMI, DHA, smoking status, and smoking status*ALA interaction significantly predicted SBP (p < 0.0001, R2 = 0.44) and DBP (p < 0.0001, R2 = 0.33), while ethnicity had no effect. The observed lower BP when DHA levels are high suggests a possible protective role of DHA on BP in normotensive smokers and nonsmokers. Additionally, the observed higher BP when ALA levels are high only in smokers suggests that ALA may influence the BP-lowering effects of chronic smoking.

The association of maternal polyunsaturated fatty acids during pregnancy with social competence and problem behaviours at 7 years of age: The MEFAB cohort Publication date: May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 144 Author(s): E.C. Tore, M. Gielen, E.E. Antoniou, R.H.M. de Groot, R.W.L. Godschalk, T.R. Southwood, L. Smits, N. Stratakis, I.S.M. van de Wurff, M.P. Zeegers Abstract Background The prenatal exposure to maternal n-6 and n-3 polyunsaturated fatty acids (PUFAs) might influence the development of social competence and internalizing and externalizing behaviours of the child, because of the numerous functions of PUFAs within the nervous system. Methods To analyse the association of selected maternal PUFAs (i.e., AA, EPA, DHA, total n-6, total n-3, and the n-6:n-3 ratio) measured during gestation with childhood social competence and problem behaviours, we examined 311 mother-child pairs from the Maastricht Essential Fatty Acid Birth (MEFAB) cohort. For each woman, PUFA-specific changes in relative concentrations were calculated by identifying the best-fitting curve of PUFA concentration by linear splines of gestational age. The associations of changes in maternal PUFAs in early and late pregnancy with childhood social competence, total problems, internalizing and externalizing behaviours, measured with the Child Behaviour Checklist 4/18 at age 7, were investigated with linear regression analyses adjusted for maternal and children's socio-demographic characteristics. Results In late gestation (i.e., from gestational week 30), an increase in AA was associated with higher social competence, while a decrease in total n-6 was associated with lower externalizing behaviours. No other significant associations were found. Discussion In this prospective study, increasing maternal AA and decreasing total n-6 were associated with improved social competence and externalizing behaviours, respectively, in 7-year old children. Nonetheless, the clinical significance of the identified associations is modest and further investigations are warranted to clarify the relationship between maternal AA and total n-6 during pregnancy and childhood social and behavioural development.

Editorial Board Publication date: May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 144 Author(s):

Dietary docosahexaenoic acid contributes to increased bone mineral accretion and strength in young female Sprague-Dawley rats Publication date: May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 144 Author(s): Zahra Farahnak, Marie Therese Freundorfer, Paula Lavery, Hope A. Weiler Abstract Growing evidence suggests that docosahexaenoic acid (DHA: 22:6n-3) enhances bone mineral content (BMC) and bone mineral density (BMD) in adulthood and during aging, however the effects during and after sexual maturation are unclear. The aim of this study was to examine the dose-response of BMC, BMD and microarchitectural properties of bone to dietary DHA in healthy growing female rats during acquisition of peak bone mass (PBM). Female Sprague-Dawley rats (n = 12/diet) were randomized to receive a control diet (AIN-93 M, 60 g soybean oil/kg diet) or an experimental diet containing 0.1, 0.4, 0.8 and 1.2% DHA (w/w of total diet) for 10 weeks. Dietary DHA increased the whole body, lumbar spine and long bone BMC compared to the control, in addition to higher aBMD and also BMD. Additionally, an increase in cortical bone microarchitecture parameters of lumbar spine as well as peak force were observed in dietary DHA diet groups. Dietary DHA contributes to PBM when consumed during and after sexual maturation, however higher doses of DHA do not provide further benefits.

Changes to breast milk fatty acid composition during storage, handling and processing: a systematic review Publication date: Available online 1 May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Chang Gao, Jacqueline Miller, Philippa F. Middleton, Yi-Chao Huang, Andrew J. McPhee, Robert A. Gibson Abstract This review evaluated the effect of various storage and handling conditions on the fat composition of expressed breast milk (EBM). Three databases PubMed, Embase and Scopus were searched in April 2019 with words from the three key components: human milk, handling process (i.e. storage and/or pasteurization), and fatty acid composition. The comparisons were EBM subjected to handling processes versus fresh EBM or versus EBM subjected to another handling processes. Both intervention and observational studies were included, and the outcomes measured included total fat and lipid classes of the EBM. We included 42 studies (43 reports), 40 of which were assessed to be of good quality. Relative changes to the fat composition of EBM subjected to handling processes were calculated based on the data provided in the included studies, and the results were synthesized narratively. The total fat content and total fatty acid composition of EBM was not generally influenced by storage and handling process, with most changes less than 10%, which is likely a result of methodological variation. A reduction in EBM triglyceride concentration and concomitant increase in free fatty acid concentration were seen after exposing to various conditions, probably due to endogenous lipase. Summary Our systematic review suggests that the total fat content of breast milk and its fatty acid composition are not affected by any storage or handling processes, where changes were seen they mostly less than 10% and likely due to methodological errors. However, the studies reviewed suggest that the lipid classes of breast milk are affected by storage, pasteurization, and various thawing and warming methods perhaps due to the presence of lipases. There are needs for developing clinical guidelines on handling expressed breast milk for better preserving the fat composition and developing modern technologies for more precise measurements of the changes to breast milk fat composition.