Oxylipin secretion by human CD3 T lymphocytes is modified by the exogenous essential fatty acid ratio and life stage.

Immune function changes across the life stages; for example, senior adults exhibit a tendency towards a weaker cell-mediated immune response and a stronger inflammatory response than younger adults. This might be partly mediated by changes in oxylipin synthesis across the life course. Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that modulate immune function and inflammation.

Exogenous tetracosahexaenoic acid modifies the fatty acid composition of human primary T lymphocytes and Jurkat T cell leukemia cells contingent on cell type.

Tetracosahexaenoic acid (24:6ω-3) is an intermediate in the conversion of 18:3ω-3 to 22:6ω-3 in mammals. There is limited information about whether cells can assimilate and metabolize exogenous 24:6ω-3. This study compared the effect of incubation with 24:6ω-3 on the fatty acid composition of two related cell types, primary CD3 T lymphocytes and Jurkat T cell leukemia, which differ in the integrity of the polyunsaturated fatty acid (PUFA) biosynthesis pathway.

Fatty acid composition and metabolic partitioning of α-linolenic acid are contingent on life stage in human CD3 T lymphocytes.

Introduction: Immune function changes across the life course; the fetal immune system is characterised by tolerance while that of seniors is less able to respond effectively to antigens and is more pro-inflammatory than in younger adults. Lipids are involved centrally in immune function but there is limited information about how T cell lipid metabolism changes during the life course.

Methods And Results: We investigated whether life stage alters fatty acid composition, lipid droplet content and α-linolenic acid (18:3ω-3) metabolism in human fetal CD3 T lymphocytes and in CD3 T lymphocytes from adults (median 41 years) and seniors (median 70 years).

α-linolenic acid interconversion is sufficient as a source of longer chain ω-3 polyunsaturated fatty acids in humans: An opinion.

α-linolenic acid (αLNA) conversion into the functionally important ω-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), has been regarded as inadequate for meeting nutritional requirements for these PUFA. This view is based on findings of small αLNA supplementation trials and stable isotope tracer studies that have been interpreted as indicating human capacity for EPA and, in particular, DHA synthesis is limited. The purpose of this review is to re-evaluate this interpretation.

The Partitioning of Newly Assimilated Linoleic and α-Linolenic Acids Between Synthesis of Longer-Chain Polyunsaturated Fatty Acids and Hydroxyoctadecaenoic Acids Is a Putative Branch Point in T-Cell Essential Fatty Acid Metabolism.

Longer-chain polyunsaturated fatty acids (LCPUFAs) ≥20 carbons long are required for leukocyte function. These can be obtained from the diet, but there is some evidence that leukocytes can convert essential fatty acids (EFAs) into LCPUFAs. We used stable isotope tracers to investigate LCPUFA biosynthesis and the effect of different EFA substrate ratios in human T lymphocytes.

Dietary Supplementation with Transgenic Oil Containing 20:5n-3 and 22:6n-3 or Fish Oil Induces Differential Changes in the Transcriptome of CD3 T Lymphocytes.

Eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) are important for leukocyte function. This study investigated whether consuming transgenic (tO) seed oil containing both 20:5n-3 and 22:6n-3 is as effective as fish oil (FO) for increasing the 20:5n-3 and 22:6n-3 content of leukocytes and altering mitogen-induced changes to the T cell transcriptome. Healthy adults ( = 31) consumed 450 mg/day of 20:5n-3 plus 22:6n-3 from either FO or tO for 8 weeks.

Influence of Maternal Lifestyle and Diet on Perinatal DNA Methylation Signatures Associated With Childhood Arterial Stiffness at 8 to 9 Years.

[Figure: see text].

Lipidomic Analysis of Plasma from Healthy Men and Women Shows Phospholipid Class and Molecular Species Differences between Sexes.

The phospholipid composition of lipoproteins is determined by the specificity of hepatic phospholipid biosynthesis. Plasma phospholipid 20:4n-6 and 22:6n-3 concentrations are higher in women than in men. We used this sex difference in a lipidomics analysis of the impact of endocrine factors on the phospholipid class and molecular species composition of fasting plasma from young men and women.

Maternal dysglycaemia, changes in the infant's epigenome modified with a diet and physical activity intervention in pregnancy: Secondary analysis of a randomised control trial.

Background: Higher maternal plasma glucose (PG) concentrations, even below gestational diabetes mellitus (GDM) thresholds, are associated with adverse offspring outcomes, with DNA methylation proposed as a mediating mechanism. Here, we examined the relationships between maternal dysglycaemia at 24 to 28 weeks' gestation and DNA methylation in neonates and whether a dietary and physical activity intervention in pregnant women with obesity modified the methylation signatures associated with maternal dysglycaemia.

Methods And Findings: We investigated 557 women, recruited between 2009 and 2014 from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), a randomised controlled trial (RCT), of a lifestyle intervention (low glycaemic index (GI) diet plus physical activity) in pregnant women with obesity (294 contol, 263 intervention).

Folic Acid Induces Intake-Related Changes in the Mammary Tissue Transcriptome of C57BL/6 Mice.

Folic acid (FA) intake has been associated with increased breast cancer risk in some studies. Although underlying mechanisms are unknown, epigenetic modifications that persistently alter transcription have been suggested. We tested the hypothesis that high FA (HFA) intake alters the adult mammary transcriptome in a manner consistent with increased potential for carcinogenesis, detectable beyond the period of intake.

Machine Learning-Based DNA Methylation Score for Fetal Exposure to Maternal Smoking: Development and Validation in Samples Collected from Adolescents and Adults.

Background: Fetal exposure to maternal smoking during pregnancy is associated with the development of noncommunicable diseases in the offspring. Maternal smoking may induce such long-term effects through persistent changes in the DNA methylome, which therefore hold the potential to be used as a biomarker of this early life exposure. With declining costs for measuring DNA methylation, we aimed to develop a DNA methylation score that can be used on adolescent DNA methylation data and thereby generate a score for cigarette smoke exposure.

Dietary supplementation with seed oil from transgenic induces similar increments in plasma and erythrocyte DHA and EPA to fish oil in healthy humans.

EPA and DHA are required for normal cell function and can also induce health benefits. Oily fish are the main source of EPA and DHA for human consumption. However, food choices and concerns about the sustainability of marine fish stocks limit the effectiveness of dietary recommendations for EPA + DHA intakes.

Docosahexaenoic acid and oleic acid induce altered DNA methylation of individual CpG loci in Jurkat T cells.

Docosahexaenoic acid (DHA, 22:6n-3) and oleic acid (18:1n-9) can alter the DNA methylation of individual CpG loci in vivo and in vitro, although the targeting mechanism is unknown. We tested the hypothesis that the targeting of altered methylation is associated with putative transcription factor response elements (pTREs) proximal to modified loci. Jurkat cells were treated with 22:6n-3 or 18:1n-9 (both 15 μM) for eight days and DNA methylation measured using the MethylationEPIC 850K array.

Differential postprandial incorporation of 20:5n-3 and 22:6n-3 into individual plasma triacylglycerol and phosphatidylcholine molecular species in humans.

The mechanisms by which digested fat is absorbed and transported in the circulation are well documented. However, it is uncertain whether the molecular species composition of dietary fats influences the molecular species composition of meal-derived lipids in blood. This may be important because enzymes that remove meal-derived fatty acids from the circulation exhibit differential activities towards individual lipid molecular species.

Vegetarian Diet during Pregnancy Is Not Associated with Poorer Cognitive Performance in Children at Age 6-7 Years.

Compared with omnivorous mothers, vegetarian mothers have lower intakes of some nutrients required for neurological development. However, there is a lack of information about the impact of vegetarianism during pregnancy on subsequent cognitive function in children. The aim of this study was to investigate whether vegetarianism during pregnancy is associated with altered maternal nutritional status and with cognitive function in children at six to seven years of age.

Dietary Fish Oil Alters DNA Methylation of Genes Involved in Polyunsaturated Fatty Acid Biosynthesis in Muscle and Liver of Atlantic Salmon (Salmo salar).

Adequate dietary supply of eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) is required to maintain health and growth of Atlantic salmon (Salmo salar). However, salmon can also convert α-linolenic acid (18:3n-3) into eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) by sequential desaturation and elongation reactions, which can be modified by 20:5n-3 and 22:6n-3 intake. In mammals, dietary 20:5n-3 + 22:6n-3 intake can modify Fads2 expression (Δ6 desaturase) via altered DNA methylation of its promoter.

Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic Risk.

Several studies have shown effects of current and maternal smoking during pregnancy on DNA methylation of CpG sites in newborns and later in life. Here, we hypothesized that there are long-term and persistent epigenetic effects following maternal smoking during pregnancy on adolescent offspring DNA methylation, independent of paternal and postnatal smoke exposure. Furthermore, we explored the association between DNA methylation and cardiometabolic risk factors at 17 years of age.

Preterm Birth: A Narrative Review of the Current Evidence on Nutritional and Bioactive Solutions for Risk Reduction.

Preterm birth (PTB) (<37 weeks of gestation) is the leading cause of newborn death and a risk factor for short and long-term adverse health outcomes. Most cases are of unknown cause. Although the mechanisms triggering PTB remain unclear, an inappropriate increase in net inflammatory load seems to be key.

Postprandial incorporation of EPA and DHA from transgenic Camelina sativa oil into blood lipids is equivalent to that from fish oil in healthy humans.

EPA and DHA are important components of cell membranes. Since humans have limited ability for EPA and DHA synthesis, these must be obtained from the diet, primarily from oily fish. Dietary EPA and DHA intakes are constrained by the size of fish stocks and by food choice.

Is essential fatty acid interconversion an important source of PUFA in humans?

Humans can obtain pre-formed long-chain PUFA from the diet and are also able to convert essential fatty acids (EFA) to longer-chain PUFA. The metabolic pathway responsible for EFA interconversion involves alternating desaturation and carbon chain elongation reactions, and carbon chain shortening by peroxisomal β-oxidation. Studies using stable isotope tracers or diets supplemented with EFA show that capacity for PUFA synthesis is limited in humans, such that DHA (22 : 6n-3) synthesis in men is negligible.

Arachidonic acid and DHA status in pregnant women is not associated with cognitive performance of their children at 4 or 6-7 years.

Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6-7 years in 724 mother-child pairs from the Southampton Women's Survey cohort.

Polyunsaturated Fatty Acid Biosynthesis Involving Δ8 Desaturation and Differential DNA Methylation of Regulates Proliferation of Human Peripheral Blood Mononuclear Cells.

Polyunsaturated fatty acids (PUFAs) are important for immune function. Limited evidence indicates that immune cell activation involves endogenous PUFA synthesis, but this has not been characterised. To address this, we measured metabolism of 18:3n-3 in quiescent and activated peripheral blood mononuclear cells (PBMCs), and in Jurkat T cell leukaemia.

Long-chain -3 PUFA in vegetarian women: a metabolic perspective.

Vegetarian diets have been associated with health benefits, but paradoxically are low in EPA and DHA which are important for development, particularly of the central nervous system, and for health. Humans have limited capacity for synthesis of EPA and DHA from α-linolenic acid, although this is greater in women than men. Oily fish and, to a lesser extent, dairy foods and meat are the primary sources of EPA and DHA in the diet.