Docosahexaenoic acid varies in rat skeletal muscle membranes according to fibre type and provision of dietary fish oil Publication date: December 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 151 Author(s): M.J. Macartney, G.E. Peoples, T.M. Treweek, P.L. McLennan Abstract Background Dietary fish oil provides polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and is associated with modified oxygen consumption, contractile fatigue and physiological responses to ischaemia or hypoxia in striated muscle. This study systematically investigated the membrane incorporation of fatty acids, with a focus on DHA, into skeletal muscle in relation to functional/metabolic differences and their responsiveness to fish oil doses. Methods Male Sprague-Dawley rats were randomised to isoenergetic diets (10% fat by weight). Human Western-style diets were simulated with 5.5% tallow, 2.5% n-6 PUFA sunflower seed oil and 2% olive oil (Control). High-DHA tuna oil exchanged for olive oil provided a Low (0.32%) or moderate (Mod) (1.25%) fish oil diet. Membrane phospholipid fatty acid composition was analysed in samples of five skeletal muscles selected for maximum variation in muscle fibre-type. Results Concentrations of DHA varied according to muscle fibre type, very strongly associated with fast oxidative glycolytic fibre population (r2 = 0.93; P < 0.01). No relationship was evident between DHA and fast glycolytic or slow oxidative fibre populations. Fish oil diets increased membrane incorporation of DHA in all muscles, mainly at the expense of n-6 PUFA linoleic and arachidonic acid. Conclusion The exquisite responsiveness of all skeletal muscles to as little fish oil as the equivalent of 1–2 fish meals per week in a human diet and the selective relationship to fatigable muscle fibre-types supports an integral role for DHA in muscle physiology, and particularly in fatigue resistance of fast-twitch muscles. Summary Skeletal muscle fibres vary according to structural, metabolic and neurological characteristics and ultimately influences contractile function. This study sort to determine if the composition of phospholipid polyunsaturated fatty acids (PUFA), incorporated in their membranes, might also differ according to fibre type and when omega-3 PUFA are made available in the diet. We systematically demonstrated that the omega-3 PUFA, docosahexaenoic acid (DHA), incorporated into skeletal muscle membranes well above its provision in the diet and without competitive influence of high omega-6 PUFA concentrations, typical to the Western-style human diet. Notably, incorporation preferentially occurred according to metabolic characteristics of each muscle, supporting the notion that DHA plays an integral role in fast oxidative glycolytic muscle fibres.

An abundance of seafood consumption studies presents new opportunities to evaluate effects on neurocognitive development Publication date: December 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 151 Author(s): Philip Spiller, Joseph R. Hibbeln, Gary Myers, Gretchen Vannice, Jean Golding, Michael A Crawford, J.J. Strain, Sonja L. Connor, J. Thomas Brenna, Penny Kris-Etherton, Bruce J. Holub, William S. Harris, Bill Lands, Robert K. McNamara, Michael F. Tlusty, Norman Salem, Susan E. Carlson Abstract The relationship between seafood eaten during pregnancy and neurocognition in offspring has been the subject of considerable scientific study for over 25 years. Evaluation of this question led two scientific advisory committees to the Dietary Guidelines for Americans (DGAC), the Food and Agriculture Organization of the United Nations with the World Health Organization (FAO/WHO), Health Canada, the European Food Safety Authority (EFSA), and the U.S. Food and Drug Administration (FDA) to conclude through 2014 that seafood consumed by pregnant women is likely to benefit the neurocognitive development of their children. The evidence they reviewed included between four and ten studies of seafood consumption during pregnancy that reported beneficial associations. In contrast there are now 29 seafood consumption studies available describing over 100,000 mothers-child pairs and 15 studies describing over 25,000 children who ate seafood. A systematic review of these studies using Nutrition Evaluation Systematic Review methodology is warranted to determine whether recent research corroborates, builds on, or significantly alters the previous conclusions. Studies that evaluate the integrated effects of seafood as a complete food more directly and completely evaluate impacts on neurocognition as compared to studies that evaluate individual nutritients or toxicological constituents in isolation. Here we address how the findings could add to our understanding of whether seafood consumed during pregnancy and early childhood affects neurocognition, including whether such effects are clinically meaningful, lasting, related to amounts consumed, and affected by any neurotoxicants that may be present, particularly mercury, which is present at varying levels in essentially all seafood. We provide the history, context and rationale for reexamining these questions in light of currently available data.

Effects of prostaglandin E2 and D2 on cell proliferation and osteogenic capacity of human mesenchymal stem cells Publication date: December 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 151 Author(s): C. Ern, I. Frasheri, T. Berger, H.G. Kirchner, R. Heym, R. Hickel, M. Folwaczny Abstract The manifestation of periodontitis-related inflammatory reaction is inevitably bound to the production of prostaglandins E2 and D2 which have been suggested to mediate osteoclastic and osteogenic effects within the affected tissue. We demonstrated the presence of PGE2 and PGD2 receptors on hMSCs on RNA level and with immunofluorescence. For each Prostaglandin, three concentrations were studied: 0.1; 0.5 or 1.0 µg/ml. A lower expression of EP1 and EP4 (PGE2 receptors 1 and 4) after stimulation with PGE2 was shown, thus a tendency to compromise osteogenic differentiation and metabolism. PGE2 induced a higher growth-rate during the first week, while a continuous inflammatory challenge determined a decrease of the proliferation of hMSCs. PGD2 inhibited cell growth irrespective of the duration of the stimulation. PGE2 and PGD2 have also negative effects on calcium deposition osteogenic, thus on differentiation of hMSCs. PGE2 and PGD2 seem to induce bone resorption also having indirectly a negative impact on the osteogenic differentiation of hMSCs. Thus, inhibitors of PGE2 and PGD2 can be used as adjunct to mechanical periodontal treatment.

Relationships between seafood consumption during pregnancy and childhood and neurocognitive development: Two systematic reviews Publication date: December 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 151 Author(s): CAPT Joseph R. Hibbeln, Philip Spiller, J. Thomas Brenna, Jean Golding, Bruce J. Holub, William S. Harris, Penny Kris-Etherton, Bill Lands, Sonja L. Connor, Gary Myers, J.J. Strain, Michael A Crawford, Susan E. Carlson Abstract Abundant data are now available to evaluate relationships between seafood consumption in pregnancy and childhood and neurocognitive development. We conducted two systematic reviews utilizing methodologies detailed by the Dietary Guidelines for Americans Scientific Advisory Committee 2020–2025. After reviewing 44 publications on 102,944 mother-offspring pairs and 25,031 children, our technical expert committee developed two conclusion statements that included the following: “Moderate and consistent evidence indicates that consumption of a wide range of amounts and types of commercially available seafood during pregnancy is associated with improved neurocognitive development of offspring as compared to eating no seafood. Overall, benefits to neurocognitive development began at the lowest amounts of seafood consumed (∼4 oz/wk) and continued through the highest amounts, above 12 oz/wk, some range up to >100 oz/wk.”, “This evidence does not meet the criteria for “strong evidence” only due to a paucity of randomized controlled trials that may not be ethical or feasible to conduct for pregnancy” and “Moderate and consistent evidence indicates that consumption of >4 oz/wk and likely >12 oz/wk of seafood during childhood has beneficial associations with neurocognitive outcomes.” No net adverse neurocognitive outcomes were reported among offspring at the highest ranges of seafood intakes despite associated increases in mercury exposures. Data are insufficient for conclusive statements regarding lactation, optimal amounts, categories or specific species characterized by mercury content and neurocognitive development; although there is some evidence that dark/oily seafood may be more beneficial. Research was conducted in healthy women and children and is generalizable to US populations. Assessment of seafood as a whole food integrates inherently integrates any adverse effects from neurotoxicants, if any, and benefits to neurocognition from omega-3 fats, as well as other nutrients critical to optimal neurological development. Understanding of the effects of seafood consumption on neurocognition can have significant public health implications.

Loss of RAR-related orphan receptor Alpha (RORα) selectively lowers docosahexaenoic acid in developing cerebellum Publication date: Available online 20 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Chuck T. Chen, Joseph A. Schultz, Sophie E. Haven, Breanne Wilhite, Chi-Hsiu Liu, Jing Chen, Joseph R. Hibbeln Abstract Deficiency in retinoid acid receptor-related orphan receptor alpha (RORα) of staggerer mice results in extensive granule and Purkinje cell loss in the cerebellum as well as in learned motor deficits, cognition impairments and perseverative tendencies that are commonly observed in autistic spectrum disorder (ASD). The effects of RORα on brain lipid metabolism associated with cerebellar atrophy remain unexplored. The aim of this study is to examine the effects of RORα deficiency on brain phospholipid fatty acid concentrations and compositions. Staggerer mice (Rorasg/sg) and wildtype littermates (Rora+/+) were fed n-3 polyunsaturated fatty acids (PUFA) containing diets ad libitum. At 2 months and 7 or more months old, brain total phospholipids fatty acids were quantified by gas chromatography-flame ionization detection. In the cerebellum, all fatty acid concentrations were reduced in 2 months old mice. Since total fatty acid concentrations were significantly different at 2-month-old, we examined changes in fatty acid composition. The composition of ARA was not significantly different between genotypes; though DHA composition remained significantly lowered. Despite cerebellar atrophy at >7-months-old, cerebellar fatty acid concentrations had recovered comparably to wildtype control. Therefore, RORα may be necessary for fatty acid accretions during neurodevelopment. Specifically, the effects of RORα on PUFA metabolisms are region-specific and age-dependent.

Comparison of dietary and plasma phospholipid fatty acids between normal weight and overweight black South Africans according to metabolic health: The PURE study Publication date: Available online 19 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): AA Ojwang, CM Smuts, M Zec, E Wentzel-Viljoen, IM Kruger, HS Kruger Abstract Background Information regarding circulating fatty acids (FA) in association with metabolic health in black Africans is scarce, while the usefulness of circulating FAs as biomarkers of dietary fat intake and predictors for medical conditions is increasing. Objective We compared eleven dietary and the levels of 26 plasma phospholipid FAs in metabolically healthy and unhealthy phenotypes in black South African adults. Methods Adults from the South African arm of the Prospective Urban and Rural Epidemiology study baseline (n=711) were categorised into four groups, namely normal weight without metabolic syndrome (MetS) (MHNW), normal weight with MetS (MUNW), metabolically healthy overweight/obese (MHO) and metabolically unhealthy overweight/obese (MUO). Dietary and plasma phospholipid FAs were measured by a quantitative food frequency questionnaire and gas chromatography-tandem mass spectrometry, respectively. We compared dietary FAs, plasma phospholipid FAs, and estimated desaturase activity between the metabolic status groups using ANCOVA adjusted for age and energy intake. Results MetS was diagnosed in 35% of the participants. After adjustment for age and total energy intake, in comparison to the MHNW reference group, saturated dietary FAs (C14:0 to C18:0) and alpha-linolenic acid intakes were higher in both overweight/obese groups (MHO and MUO), while linoleic acid intakes were higher in the MUO group only. Plasma levels of most saturated FAs (C18:0 to C22:0) and PUFAs were higher, whereas selected MUFAs, palmitic acid, and estimated desaturase activities were lower in the overweight/obese groups. Conclusions The overweight groups generally had higher fat intakes than normal-weight groups, but lower plasma levels of palmitic, palmitoleic, oleic, cis-vaccenic and estimated desaturase activities. Therefore, in this population, lower plasma levels of palmitic, palmitoleic, oleic, and cis-vaccenic acids and decreased estimated desaturase activities may be biomarkers of abnormal metabolic health in overweight/obese study participants.

Serum concentration of dihomo-γ-linolenic acid is associated with cognitive function and mild cognitive impairment in coronary artery disease patients Publication date: Available online 16 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Kodai Ishihara, Kazuhiro P. Izawa, Masahiro Kitamura, Takayuki Shimogai, Yuji Kanejima, Tomoyuki Morisawa, Ikki Shimizu Abstract Background The relation between levels of n-6 polyunsaturated fatty acids (PUFAs) and cognitive function and mild cognitive impairment (MCI) in patients with coronary artery disease (CAD) is unclear. The purpose of the present study was to examine the associations between levels of n-6 PUFAs and cognitive function and MCI in patients with CAD. Methods We conducted a cross-sectional study of 129 patients with CAD but without probable dementia. MCI was estimated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J). We classified patients into the normal cognitive group and MCI group and compared their clinical characteristics and serum levels of PUFAs. The relation between these levels and cognitive function and MCI was clarified with Pearson correlation analysis and logistic regression analysis. Results The serum levels of dihomo-γ-linolenic acid (DGLA) in the CAD patients with MCI were significantly lower than those in the patients with normal cognitive function (p= 0.04). The serum levels of DGLA were positively associated with the MoCA-J score (r= 0.24, p= 0.005) and significantly associated with MCI in the univariate logistic regression analysis (odds ratio, 0.97; p= 0.035). However, in the multivariate logistic regression analysis, only age was significantly associated with MCI (odds ratio, 1.11; p < 0.001). Conclusions The serum levels of DGLA were associated with cognitive function and MCI in patients with CAD. Although not an independent predictor, DGLA might be one useful marker with which to identify early cognitive decline in these patients.

A simple system for measuring the level of free fatty acids in human milk collected as dried milk spot Publication date: Available online 14 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Chang Gao, Ge Liu, Andrew J. McPhee, Jaqueline Miller, Robert A. Gibson Abstract Breast milk dried on filter paper is a useful collection device for the study of breast milk because it avoids the costs associated with cold-chain storage and transportation. Although the fatty acid profile of breast milks as dried spots is stable, changes to the composition of lipid classes of breast milk due to lipase activity have been reported and are best reflected by its free fatty acid (FFA) concentration. This study aimed to develop a robust dried milk spot (DMS) system where fats in the breast milk are stable at room temperature, and the FFA concentration of the milk can be accurately measured without interference by the high level of triglyceride, which normally constitutes around 98% of the fats in fresh milk. Our system involves applying a small amount breast milk (20 µL) on silica gel impregnated filter paper and microwaving at high power to denature lipases. At the time of analysis, the milk fats are eluted with acetone, re-constituted in heptane and injected directly into a gas chromatograph equipped with an acid modified polyethylene glycol column. This DMS method was validated against the conventional TLC method across a range of FFA concentrations. The breast milk fats collected using this DMS system are stable at room temperature for at least eight weeks which allows for transportation by post and has the potential for use in multi-centred international clinical trials.

Different metabolism of EPA, DPA and DHA in humans: A double-blind cross-over study Publication date: Available online 12 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Xiao-fei Guo, Wen-feng Tong, Yue Ruan, Andrew J. Sinclair, Duo Li Abstract This study aimed to compare eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) incorporated into red blood cells (RBC) phospholipids (PL), plasma PL, plasma triglyceride (TAG), and plasma cholesteryl ester (CE) fractions, and the metabolomics profiles in a double-blind cross-over study. Twelve female healthy subjects randomly consumed 1 g per day for 6 days of pure EPA, DPA, or DHA. The placebo treatment was olive oil. The fasting venous blood was taken at days 0, 3 and 6, and the RBC PL and plasma lipid fractions were separated for fatty acid determination using thin layer chromatography followed by gas chromatography. Plasma metabolites were analyzed by UHPLC-Q-Exactive Orbitrap/MS. Supplemental EPA significantly increased the concentrations of EPA in RBC PL (days 3 and 6). For subjects consuming the DPA supplement, the concentrations of both DPA and EPA were significantly increased in RBC PL over a 6-day period, respectively. For plasma PL fraction, EPA and DPA supplementation significantly increased the concentrations of EPA and DPA at both days 3 and 6, respectively. Supplemental DHA significantly increased the concentrations of DHA in plasma PL at day 6. For plasma TAG fraction, supplementation with EPA and DPA significantly increased the concentrations of EPA and DPA at both days 3 and 6, respectively. After DHA supplementation, significant increases in the concentrations of DHA were found relative to baseline at both days 3 and 6. For plasma CE fraction, EPA supplementation significantly increased the concentrations of EPA (days 3 and 6) and DPA (days 6), respectively. Supplemental DPA significantly increased the concentrations of EPA at day 6. Meanwhile, the concentrations of DHA were significantly increased over a 6-day period of intervention after subjects consuming the DHA supplements. There were a total of 922 plasma metabolites identified using metabolomics analyses. Supplementation with DPA and DHA significantly increased the levels of sphingosine 1-phosphate (P for DPA = 0.025, P for DHA = 0.029) and 15-deoxy-Δ12,14-prostaglandin A1 (P for DPA = 0.034; P for DHA = 0.021) in comparison with olive oil group. Additionally, supplementation with EPA (P = 0.007) and DHA (P = 0.005) significantly reduced the levels of linoleyl carnitine, compared with olive oil group. This study shows that DPA might act as a reservoir of n-3 LCP incorporated into blood lipid fractions, metabolized into DHA, and retro-converted back to EPA. Metabolomics analyses indicate that supplemental EPA, DPA and DHA have shared and differentiated metabolites. The differences of these metabolic biomarkers should be investigated in additional studies.

Development and evaluation of a simultaneous and efficient quantification strategy for final prostanoid metabolites in urine Publication date: Available online 6 November 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Tian-qi Zhang, Hirotaka Kuroda, Kazuya Nagano, Soshi Terada, Jian-Qing Gao, Kazuo Harada, Kazumasa Hirata, Hirofumi Tsujino, Kazuma Higashisaka, Hiroshi Matsumoto, Yasuo Tsutsumi Abstract Prostanoids (PNs) play critical roles in various physiological and pathological processes. Therefore, it is important to understand the alternation of PN expression profiles. However, a simultaneous and efficient quantification system for final PN metabolites in urine has not yet been established. Here, we developed and evaluated a novel method to quantify all final PN metabolites. By purification using a reverse phase solid phase extraction (SPE) column, the matrix effects against the final PGD2, PGE2, and PGF2α metabolites were low, and their accuracies were nearly 100%. The matrix effects against the final PGI2 and TXA2 metabolites were high using reverse phase SPE column purification alone. By applying a tandem SPE method that combined reverse phase and ion exchange SPE columns, the matrix effects decreased so that the accuracy was nearly 100%. To validate the reliability of the method, each final metabolite was quantified from mouse urine to which the PNs (PGD2, PGE2, and PGI2) were intravenously administered. As a result, the amounts of PN metabolites were correlated with those of the PNs administered to the blood in a dose-dependent manner. To validate the method using human samples, the urinary metabolites of Crohn's disease (CD, a PN-related disease) patients and healthy individuals were quantified. All five metabolites were successfully quantified. Only final PGE2 metabolite levels were significantly higher in CD patients than those in healthy individuals, so that the urinary metabolite profiles of CD patients is determined. In conclusion, we developed a novel method to quantify all final PN metabolites simultaneously and efficiently and demonstrated the practicality of the method using human CD patient samples.