Polyunsaturated Fatty Acids In Phospholipids Research Articles

The PRMT6/STAT1/ACSL1 axis promotes ferroptosis in diabetic nephropathy.

Hyperglycaemia-induced ferroptosis is a significant contributor to kidney dysfunction in diabetic nephropathy (DN) patients. In addition, targeting ferroptosis has clinical implications for the treatment of DN. However, effective therapeutic targets for ferroptosis have not been identified. In this study, we aimed to explore the precise role of protein arginine methyltransferase 6 (PRMT6) in regulating ferroptosis in DN. In the present study, we utilized a mouse DN model consisting of both wild-type and PRMT6-knockout (PRMT6-/-) mice. Transcriptomic and lipidomic analyses, along with various molecular biological methodologies, were used to determine the potential mechanism by which PRMT6 regulates ferroptosis in DN. Our results indicate that PRMT6 downregulation participates in kidney dysfunction and renal cell death via the modulation of ferroptosis in DN. Moreover, PRMT6 reduction induced lipid peroxidation by upregulating acyl-CoA synthetase long-chain family member 1 (ACSL1) expression, ultimately contributing to ferroptosis. Furthermore, we investigated the molecular mechanism by which PRMT6 interacts with signal transducer and activator of transcription 1 (STAT1) to jointly regulate ACSL1 transcription. Additionally, treatment with the STAT1-specific inhibitor fludarabine delayed DN progression. Furthermore, we observed that PRMT6 and STAT1 synergistically regulate ACSL1 transcription to mediate ferroptosis in hyperglycaemic cells. Our study demonstrated that PRMT6 and STAT1 comodulate ACSL1 transcription to induce the production of phospholipid-polyunsaturated fatty acids (PL-PUFAs), thus participating in ferroptosis in DN. These findings suggest that the PRMT6/STAT1/ACSL1 axis is a new therapeutic target for the prevention and treatment of DN.

Lipoprotein Lipidomics as a Frontier in Non-Alcoholic Fatty Liver Disease Biomarker Discovery.

Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease characterized by the build-up of fat in the liver of individuals in the absence of alcohol consumption. This condition has become a burden in modern societies aggravated by the lack of appropriate predictive biomarkers (other than liver biopsy). To better understand this disease and to find appropriate biomarkers, a new technology has emerged in the last two decades with the ability to explore the unmapped role of lipids in this disease: lipidomics. This technology, based on the combination of chromatography and mass spectrometry, has been extensively used to explore the lipid metabolism of NAFLD. In this review, we aim to summarize the knowledge gained through lipidomics assays exploring tissues, plasma, and lipoproteins from individuals with NAFLD. Our goal is to identify common features and active pathways that could facilitate the finding of a reliable biomarker from this field. The most frequent observation was a variable decrease (1-9%) in polyunsaturated fatty acids in phospholipids and non-esterified fatty acids in NAFLD patients, both in plasma and liver. Additionally, a reduction in phosphatidylcholines is a common feature in the liver. Due to the scarcity of studies, further research is needed to properly detect lipoprotein, plasma, and tissue lipid signatures of NAFLD etiologies, and NAFLD subtypes, and to define the relevance of this technology in disease management strategies in the push toward personalized medicine.

Eicosapentaenoic acid and Arachidonic acid Protection Against Left Ventricle Pathology: the Multi-Ethnic Study of Atherosclerosis.

We have shown that ω3 polyunsaturated fatty acids (PUFAs) reduce risk for heart failure, regardless of ejection fraction status. Ventricular remodeling and reduced ventricular performance precede overt hear failure, however there is little insight into how PUFAs contribute to maladaptive signaling over time. PUFAs are agonists for regulatory activity at g-protein coupled receptors such as Ffar4, and downstream as substrates for monooxygenases (e.g lipoxygenase, cytochrome p450, or cyclooxygenase (COX)) which mediate intracellular adaptive signaling. Plasma phospholipid PUFA abundance at Exam 1 as mass percent EPA, DHA, and arachidonic acid (AA) from the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated using pathway modeling to determine the association with time-dependent changes in left ventricular (LV) mass (LVM), end-diastolic LV volume (EDV), and end-systolic volume (ESV) measured by cardiac MRI at Exams 1 and 5. Ejection fraction (EF) and mass:volume (MV) were calculated posteriorly from the first three. 2,877 subjects had available MRI data. Participants with low AA and EPA had accelerated age-dependent declines in LVM. Males with low AA and EPA also had accelerated declines in EDV, but among females there was no PUFA association with EDV declines and exam 5 EDV status was positively associated with AA. Both sexes had nearly the same positive association of AA with changes in ESV. Plasma phospholipid AA and EPA are prospectively associated with indices of heart remodeling, including ventricular remodeling and performance. Combined AA and EPA scarcity was associated with the most accelerated age-related changes and exam 5 status, while the greatest benefits were found among participants with both PUFAs. This suggests that both PUFAs are required for optimal slowing of age-related declines in ventricular function.

Lipidomics profile and volatile compounds of squids (Illex argentinus, Ommastrephes Bartram and Dosidicus gigas) in the Argentine, North Pacific Ocean, Equator and Peru by UPLC-triple TOF-MS and HS-SPME-GC-O-MS

Comprehensive lipid and volatile compound analyses were performed with squids collected from four varied geographical locations to discriminate the regional characteristics. A total of 1442 lipid molecules and 110 volatiles were detected in the squid muscle samples. There were significant differences in the lipid profiles between Argentine squid (Illex argentinus, AGT), North Pacific Ocean squid (Ommastrephes Bartram, NPO), Equatorial squid (Dosidicus gigas, EQ), and Peruvian squid (Dosidicus gigas, PR) muscle. Phosphatidylcholines (14.64%), triacylglycerols (12.42%), and ceramides (10.97%) were the main lipid components. The contents of polyunsaturated fatty acid in phospholipids and in glycerolipids were 30.35–52.05% and 18.11–25.15%, respectively. The volatiles in squids exhibited significant regional variation; 1-pentanol and 1-octanol, 2-ethyl-1-hexanol and terpinen-4-ol, 2,7-ethyl-1-hexanol, 3-methy-1-butanol and 2-propyl-1-pentanol were identified as characteristic flavor compounds in AGT, NPO, EQ, and PR, respectively. Sphingomyelin, phosphatidylserine, phosphatidylethanolamine, and ceramide were strongly correlated with volatiles in squid muscle. Our study is a reference for the lipid nutritional value and flavor compounds of squids.

Targeting carnitine palmitoyl transferase 1A (CPT1A) induces ferroptosis and synergizes with immunotherapy in lung cancer

Despite the successful application of immune checkpoint therapy, no response or recurrence is typical in lung cancer. Cancer stem cells (CSCs) have been identified as a crucial player in immunotherapy-related resistance. Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is highly regulated by cellular metabolism remolding and has been shown to have synergistic effects when combined with immunotherapy. Metabolic adaption of CSCs drives tumor resistance, yet the mechanisms of their ferroptosis defense in tumor immune evasion remain elusive. Here, through metabolomics, transcriptomics, a lung epithelial-specific Cpt1a-knockout mouse model, and clinical analysis, we demonstrate that CPT1A, a key rate-limiting enzyme of fatty acid oxidation, acts with L-carnitine, derived from tumor-associated macrophages to drive ferroptosis-resistance and CD8+ T cells inactivation in lung cancer. Mechanistically, CPT1A restrains ubiquitination and degradation of c-Myc, while c-Myc transcriptionally activates CPT1A expression. The CPT1A/c-Myc positive feedback loop further enhances the cellular antioxidant capacity by activating the NRF2/GPX4 system and reduces the amount of phospholipid polyunsaturated fatty acids through ACSL4 downregulating, thereby suppressing ferroptosis in CSCs. Significantly, targeting CPT1A enhances immune checkpoint blockade-induced anti-tumor immunity and tumoral ferroptosis in tumor-bearing mice. The results illustrate the potential of a mechanism-guided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CSCs to improve the efficacy of lung cancer immunotherapy.

Maternal plasma phospholipid polyunsaturated fatty acids in early pregnancy and thyroid function throughout pregnancy: a longitudinal study

BackgroundEvidence has indicated that polyunsaturated fatty acids (PUFAs)-enriched diet could reduce inflammation because of thyroid autoimmunity in vivo, and therefore, enhance thyroid function. ObjectivesWe investigated whether early pregnancy plasma phospholipid PUFAs could benefit maternal thyroid function across pregnancy, which is critical to fetal brain development and growth in pregnancy. MethodsWithin the National Institute of Child Health and Human Development Fetal Growth Studies–Singleton Cohort, we collected plasma samples longitudinally from 214 subjects [107 with gestational diabetes mellitus (GDM) matched with 107 controls] with a singleton pregnancy. We measured 11 PUFAs at early pregnancy (10–14 wk) and 5 thyroid biomarkers at 10–14, 15–26, 23–31, and 33–39 wk, including free thyroxine (fT4), free triiodothyronine (fT3), thyroid-stimulating hormone, antithyroid peroxidase, and antithyroglobulin. Associations of PUFAs with thyroid function biomarkers and relative risk (RR) of gestational hypothyroidism (GHT) during pregnancy were assessed using generalized linear mixed models and modified Poisson regression, respectively. ResultsAfter sample weighting because of subjects with GDM over-representing in the analytic sample with biomarkers, eicosapentaenoic acid (EPA) at early pregnancy was associated with a reduction of 0.24 pmol/L (95% confidence intervals: −0.31, −0.16) in fT3 across gestation per standard deviation (SD) increment, whereas docosahexaenoic acid (DHA) at early pregnancy was associated with an increment of 0.04 ng/dL (0.02, 0.05) in fT4 across gestation per SD increment. Furthermore, EPA and docosatetraenoic acid (DTA) were associated with lower risks of persistent GHT (EPA—RR: 0.13; 0.06, 0.28; DTA—RR: 0.24; 0.13, 0.44) per SD increment. All significant associations remained robust in sensitivity analysis and multiple testing. ConclusionsCertain plasma phospholipid PUFAs were associated with optimal levels of thyroid biomarkers and even lower risk of GHT throughout pregnancy, which might be potentially targeted for maternal thyroid regulation in early pregnancy. Clinical Trial RegistryThis trial was registered at https://beta.clinicaltrials.gov/study/NCT00912132?distance=50&term=NCT00912132&rank=1 as NCT00912132.

N-3 polyunsaturated fatty acids in phospholipid or triacylglycerol form attenuate nonalcoholic fatty liver disease via mediating cannabinoid receptor 1/adiponectin/ceramide pathway

n-3 polyunsaturated fatty acids (PUFA) have shown to exert beneficial effects in the treatment of nonalcoholic fatty liver disease (NAFLD). Supplements of n-3 PUFA occur in either phospholipid or triacylglycerol form. The present study aimed to compare whether the different n-3 PUFA of marine-origin, namely krill oil, DHA/EPA-phospholipid (PL), and EPA/DHA-triacylglycerol (TAG) forms had differential abilities to ameliorate NAFLD. The NAFLD model was established in mice fed a high-fat and high-cholesterol diet (HFD). The mice showed evidence of weight gain, dyslipidemia, insulin resistance and hepatic steatosis after 9 weeks of HFD, while the three forms of the n-3 PUFA reduced hepatic TAG accumulation, fatty liver and improved insulin instance, and hepatic biomarkers after 9 weeks of intervention. Of these, krill oil intervention significantly reduced adipocyte hypertrophy and hepatic steatosis in comparison with DHA/EPA-PL and EPA/DHA-TAG groups. Importantly, only krill oil intervention significantly reduced serum alanine transaminase, aspartate transaminase concentrations and low-density lipoprotein-cholesterol, compared with the HFD group. Supplemental n-3 PUFA lowered circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) concentrations, compared with the HFD group, which was associated with down-regulating CB1 and upregulating adiponectin expressions in adipose tissue. Besides, targeted lipidomic analyses indicated that the increased adiponectin levels were accompanied by reductions in hepatic ceramide levels. The reduced ceramide levels were associated with inhibiting lipid synthesis and increasing fatty acid β-oxidation, finally inhibiting TAG accumulation in the liver. Through mediating CB1/adiponectin/ceramide pathway, the present study suggested that administration of krill oil had superior health effects in the therapy of NAFLD in comparison with DHA/EPA-PL and EPA/DHA-TAG.

Effects of dietary forage-to-concentrate ratio and forage type on milk phospholipids and fatty acid composition of polar lipids

The effects of grass silage and red clover silage on milk fatty acid (FA) composition are extensively studied, but little is known of their effects on minor lipid constituents of milk fat globule membrane. We investigated the effects of forage:concentrate (FC) ratio in grass silage-based diets and forage type (grass silage vs. red clover silage) on selected molecular species of milk phospholipids (PL) and the FA composition of PL. Ten multiparous Nordic Red cows were offered following dietary treatments: grass silage-based diets containing 70:30 (HG) or 30:70 (LG) FC ratio or a red clover silage-based diet (RC) comprising 50:50 FC ratio on a dry matter basis. The most abundant molecular species within the phosphatidylcholines was 16:0-18:1 phosphatidylcholine that was increased by 18% in HG compared with LG milk. Dietary treatments did not affect the relative proportion of 18:1-18:1+18:0-18:2 phosphatidylethanolamine that was the most prevalent species (ca. 44%-45%) in that class. We identified the d18:1-22:0 sphingomyelin as the most abundant sphingomyelin species that tended to increase in HG milk compared with LG. The FC ratio did not affect the relative proportions of saturated FA nor monounsaturated FA in PL, but the proportion of cis-9 18:1 was elevated in HG versus LG milk, whereas the proportion of 18:2n-6 was 50% higher in LG versus HG milk. The RC diet increased monounsaturated FA and 18:3n-3 levels in PL compared with grass silage-based diets and decreased the relative proportion of saturated FA. However, the RC diet did not affect the relative proportion of polyunsaturated FA in PL, although red clover silage typically increases the proportion of polyunsaturated FA in milk fat. This study provides valuable knowledge of the minor lipid components in milk on species level in relation to common feeding strategies in high-forage systems.

Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36.

Lipids contribute to hematopoiesis and membrane properties and dynamics; however, little is known about the role of lipids in megakaryopoiesis. Here we show that megakaryocyte progenitors, megakaryocytes and platelets present a unique lipidome progressively enriched in polyunsaturated fatty acid (PUFA)-containing phospholipids. In vitro, inhibition of both exogenous fatty acid functionalization and uptake as well as de novo lipogenesis impaired megakaryocyte differentiation and proplatelet production. In vivo, mice on a high saturated fatty acid diet had significantly lower platelet counts, which was prevented by eating a PUFA-enriched diet. Fatty acid uptake was largely dependent on CD36, and its deletion in mice resulted in low platelets. Moreover, patients with a CD36 loss-of-function mutation exhibited thrombocytopenia and increased bleeding. Our results suggest that fatty acid uptake and regulation is essential for megakaryocyte maturation and platelet production and that changes in dietary fatty acids may be a viable target to modulate platelet counts.

P02-030-23 Plasma Phospholipid Polyunsaturated Fatty Acids in Early Pregnancy and Thyroid Function Throughout Pregnancy: A Longitudinal Study

P02-030-23 Plasma Phospholipid Polyunsaturated Fatty Acids in Early Pregnancy and Thyroid Function Throughout Pregnancy: A Longitudinal Study

Phospholipid Fatty Acid Profiles of Plasma and Erythrocyte Membranes in Dogs Fed with Commercial Granulated Food

Abstract Intake of long-chain n-3 polyunsaturated fatty acids (PUFA) benefits human and animal health. Our study aimed to analyze the long-chain n-3 PUFA content of two types of food and their effect on plasma and erythrocyte phospholipids of Belgian Shepherd dogs. A total of 10 dogs were fed commercial granulated food (Food 1), and another 10 were provided commercial Premium granulated food of high quality (Food 2). All the analyses were performed using gas-liquid chromatography. Our results showed that Food 1 contained more n-3 PUFA than Food 2, which was reflected in higher n-3 PUFA in plasma and erythrocyte phospholipids. Because long-chain n-3 PUFA in phospholipids are precursors for antioxidative molecules, further studies should investigate the effects of the analyzed commercial granulated food rich in n-3 on oxidative stress parameters in dogs.

A Soy Protein Isolate Rich in Genistein and Daidzein and Its Effects on Plasma Isoflavone Concentrations, Platelet Aggregation, Blood Lipids and Fatty Acid Composition of Plasma Phospholipid in Normal Men

The effects of consuming a soy protein isolate beverage powder (60 g/d for 28 d) vs. a casein supplement was evaluated in 20 male subjects who were randomly allocated into the two groups. A dramatic rise in plasma isoflavone concentrations was observed after supplementation in the soy protein group, the levels reaching 907 ± 245 nmol/L for genistein (a 110-fold increase) and 498 ± 102 nmol/L for daidzein (a 150-fold increase) as measured by isotope dilution gas chromatography - mass spectrometry. These concentrations are higher than previously reported for the plasma of Japanese subjects consuming a traditional diet (276 nmol/L and 107 nmol/L, respectively). No significant differences in collagen- or 9,11-dideoxy-11α, 9α-epoxymethanoprostaglandin F2α (U46619)-induced platelet aggregation were observed in platelet-rich plasma from the two groups; the increase in plasma isoflavonoids from soy protein supplementation is not sufficient to significantly inhibit platelet aggregation ex vivo. Similarly, plasma total and HDL-cholesterol were not affected by protein supplementation, possibly because the men were normo-cholesterolemic at entry. Analysis of plasma phospholipid polyunsaturated fatty acid composition showed no differences between soy protein and casein supplementation. Previous investigations reported a significant alteration in fatty acid status in animals fed soy protein relative to those fed casein. The present studies indicate that although soy protein supplementation to a typical Western diet can increase plasma concentrations of isoflavones, this may not necessarily be sufficient to counter heart disease risk factors such as high plasma cholesterol and platelet aggregation.

Synthesis and lipid-lowering effects of phospholipid-polyunsaturated fatty acids (PL-PUFA) in high fat diet induced obese mice

In this study, phospholipid-polyunsaturated fatty acids (PL-PUFA), which was a glycerophosphamide analogue containing DHA/DPA of phospholipid derivative, was synthesized from algae oil in two steps. The compound of P1/P2 in the PL-PUFA was isolated through preparative HPLC with the contained of 70.24%, and 23.86%, respectively. Intragastric administration of 200 mg/kg PL-PUFA can strongly suppress net body weight gain and obesity-related hyperlipidemia. The net body-weight gain of treatment group was decreased 5.18% than that of the normal group. Serum TC levels of treatment group were significantly suppressed, and it was reduced by 55.95%. However, for HDL-C levels, none of the model group and treatment group showed significant differences comparing with the normal group. The preliminary biological data of PL-PUFA in this work strongly supports our belief that the analogue glycerophosphamide structure containing with ω-3 PUFAs is providing a beneficial effect on lowering serum lipids and TGs.

Plasma phospholipid polyunsaturated fatty acids composition in early pregnancy and fetal growth trajectories throughout pregnancy: Findings from the US fetal growth studies-singletons cohort.

SummaryBackgroundWe aimed to investigate plasma phospholipid PUFA levels in early pregnancy and fetal growth trajectories throughout pregnancy.MethodsWithin the NICHD Fetal Growth Studies–Singleton Cohort, we enrolled 2,802 pregnant women at gestational weeks 8–13 and randomly assigned them to four ultrasonogram schedules to capture weekly fetal growth throughout pregnancy. Eleven plasma phospholipid PUFAs were measured at early pregnancy using blood samples collected from a subsample of 321 pregnant women. We modeled fetal growth trajectories across tertiles of PUFAs with cubic splines using linear mixed models after adjusting for major confounders. We then compared pairwise weekly fetal growth biometrics referencing the lowest tertile in each PUFA using the Wald test.FindingsAmong plasma n-3 PUFAs in early pregnancy, docosahexaenoic acid (DHA, 22:6n3) and alpha-linolenic acid (ALA, 18:3n3) showed positive associations with all fetal growth measurements. For instance, compared with the lowest tertile, the highest tertile of DHA had greater estimated fetal growth (EFW) and abdominal circumference (AC), starting at 13 weeks of gestation and throughout pregnancy (at gestational week 38: 3235.3 vs. 3089.0 g for EFW; 344.6 vs. 339.2 mm for AC). As for plasma n-6 PUFAs, some showed positive associations (e.g., linoleic acid [LA], 18:2n6) while others (e.g., docosatetraenoic acid [DTA], 22:4n6) showed inverse associations with fetal growth measures.InterpretationOur data suggested that higher plasma levels of DHA and ALA in the first trimester were associated with increased fetal size and weight throughout subsequent pregnancy.FundingNational Institute of Child Health and Human Development intramural funding.

Ocean Acidification Alleviates Dwarf Eelgrass (Zostera noltii) Lipid Landscape Remodeling under Warming Stress.

Simple SummaryExpected climate change scenarios will have inevitable and important impacts on key foundation marine species such as seagrasses. This study was aimed to understand how the dwarf eelgrass Zostera noltii leaf lipid landscapes are altered under predicted ocean warming (+4 °C) and acidification (ΔpH 0.4) conditions. A severe reduction in the leaf total fatty acid (FA) content was observed in seagrasses individually exposed to hypercapnic or warming conditions, and this depletion was ameliorated under combined exposure to ocean warming and acidification conditions. The tested treatments also impacted the FA composition of all lipid classes, with warming exposure leading to decreases in polyunsaturated fatty acids (PUFAs). Galactolipid remodeling seems to have key roles in the physiological changes observed in seagrasses under these tested conditions, highlighting the higher impact of warming and that the proposed stress alleviation effect induced by increased water-dissolved CO2 availability. Neutral lipids were substantially increased under warming conditions, mainly with increases in C18 FA, impairing their use as substrates to maintain the osmotic balance of the cells. Nonetheless, the pace at which ocean warming is occurring can overcome the ameliorative capacity induced by higher CO2 availability, leaving seagrasses under severe heat stress beyond their lipid-remodeling capacity.Coastal seagrass meadows provide a variety of essential ecological and economic services, including nursery grounds, sediment stabilization, nutrient cycling, coastal protection, and blue carbon sequestration. However, these ecosystems are highly threatened by ongoing climatic change. This study was aimed to understand how the dwarf eelgrass Zostera noltii leaf lipid landscapes are altered under predicted ocean warming (+4 °C) and hypercapnic (ΔpH 0.4) conditions. Warming and hypercapnic conditions were found to induce a severe reduction in the leaf total fatty acid, though the combined treatment substantially alleviated this depletion. The lipid discrimination revealed a significant increase in the relative monogalactosyldiacylglycerol (MGDG) content in both hypercapnic and warming conditions, allied to plastidial membrane stabilization mechanisms. Hypercapnia also promoted enhanced phosphatidylglycerol (PG) leaf contents, a mechanism often associated with thylakoid reinvigoration. In addition to changing the proportion of storage, galacto- and phospholipids, the tested treatments also impacted the FA composition of all lipid classes, with warming exposure leading to decreases in polyunsaturated fatty acids (PUFAs); however, the combination of both stress conditions alleviated this effect. The observed galactolipid and phospholipid PUFA decreases are compatible with a homeoviscous adaptation, allowing for the maintenance of membrane stability by counteracting excessive membrane fluidity. Neutral lipid contents were substantially increased under warming conditions, especially in C18 fatty acids (C18), impairing their use as substrates for fatty acylated derivatives essential for maintaining the osmotic balance of cells. An analysis of the phospholipid and galactolipid fatty acid profiles as a whole revealed a higher degree of discrimination, highlighting the higher impact of warming and the proposed stress alleviation effect induced by increased water-dissolved CO2 availability. Still, it is essential to remember that the pace at which the ocean is warming can overcome the ameliorative capacity induced by higher CO2 availability, leaving seagrasses under severe heat stress beyond their lipid remodeling capacity.

Plasma Phospholipid n-3/n-6 Polyunsaturated Fatty Acids and Desaturase Activities in Relation to Moderate-to-Vigorous Physical Activity through Pregnancy: A Longitudinal Study within the NICHD Fetal Growth Studies

Maternal plasma phospholipid polyunsaturated fatty acids (PUFAs) play critical roles in maternal health and fetal development. Beyond dietary factors, maternal moderate-to-vigorous physical activity (MVPA) has been linked to multiple health benefits for both the mother and offspring, but studies investigating the influence of maternal MVPA on maternal PUFA profile are scarce. The objective of present study was to examine the time-specific and prospective associations of MVPA with plasma PUFA profile among pregnant women. This study included 321 participants from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies–Singletons cohort. Maternal plasma phospholipid PUFAs and MPVA were measured at four visits during pregnancy (10–14, 15–26, 23–31, and 33–39 gestational weeks (GW)). Associations of maternal MVPA with individual plasma PUFAs and desaturase activity were examined using generalized linear models. Maternal MVPA was associated inversely with plasma phospholipid linoleic acid, gamma-linolenic acid, and Δ6-desaturase in late pregnancy (23–31 or 33–39 GW), independent of maternal age, race, education, parity, pre-pregnancy body mass index, and dietary factors. Findings from this longitudinal study indicate that maternal habitual MVPA may play a role on PUFAs metabolism, particular by alerting plasma n-6 subclass and desaturase activity in late pregnancy. These associations are novel and merit confirmation in future studies.

Spleen Oxylipin and Polyunsaturated Fatty Acid Profiles are Altered by Dietary Source of Polyunsaturated Fatty Acid and by Sex.

As the largest secondary lymphoid organ, the spleen plays an important role in immune responses. The role of arachidonic acid (ARA) and its 20-carbon eicosanoids in modulating immune function has long been of interest. However, recent advances have enabled the identification of numerous other n-6 and n-3 polyunsaturated fatty acid (PUFA)-derived oxylipins. Here, we investigate the effects of diet and sex on the spleen nonesterified oxylipin profiles and phospholipid and neutral lipid PUFA composition in Sprague-Dawley rats supplemented with oils rich in α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or linoleic acid. Dietary ALA, EPA, and DHA resulted in lower levels of ARA and ARA oxylipins. Oxylipins derived from other n-6 PUFA were also reduced despite no or opposite effect on their PUFA levels. Each diet also resulted in higher levels of oxylipins almost exclusively derived from the supplemented PUFA, despite PUFA in the same biosynthetic pathway also often being increased. Further, while oxylipin differences often reflected changes to phospholipid PUFA, there were instances where they corresponded more closely to changes in neutral lipid PUFA. With respect to sex effects, >50% of lipoxygenase ARA-derived oxylipins were higher in males in at least one diet group, while multiple DHA oxylipins were lower in males only in rats provided the DHA diet. This fundamental description of oxylipin composition in the spleen, including the influence of diet and sex and the relationship to PUFA composition, will help inform future studies examining the functions of these oxylipins under physiological and pathological conditions.

Abstract P239: Longitudinal Measurement Of Maternal Plasma Polyunsaturated Fatty Acids In Relation To Physical Activity Throughout Pregnancy-a Prospective Study Within The Nichd Fetal Growth Studies

Background: Physical activity (PA) is a key components of energy expenditure and can alter fat metabolism. Maternal polyunsaturated fatty acids (PUFA), particularly endogenous PUFA, plays critical roles on maternal health and fetal development. However, studies investigating the longitudinal association of PA with PUFA during pregnancy are scarce. Objective: To examine the prospective associations of PA with PUFA among pregnant women. Methods: This study used longitudinal data from a nested gestational diabetes mellitus case-control study (n=321) within the NICHD Fetal Growth Studies-Singletons. Plasma phospholipid PUFA and PA were measured at 4 time-points during pregnancy (10-14, 15-26, 23-31, and 33-39 GW). Total PA was calculated as energy expenditure in metabolic equivalent (METs-hour) and physically active was defined as spending ≥150 min on moderate-to-vigorous exercise per week. Associations of PA with total n-3, n-6, and individual PUFAs were examined using generalized linear models where the sample was weighted to represent the entire cohort. Results: Total PA was positively associated with EDA, but inversely associated with ALA and GLA, independent of maternal age, race, parity, pre-pregnancy BMI, and dietary intake of FA. Being physically active was inversely associated with total n-3 PUFA but positively associated with total n-6 PUFA. However, the direction of the associations of individual PUFA varied: an inverse association for ALA (n-3) and LA (n-6); a positive association for DHA (n-3), AA (n-6) and DPA (n-6). Conclusions: Findings from this study indicate that PA may alter PUFA metabolism in pregnant women. The inverse association between total PA and GLA (an endogenous PUFA) is novel and merits confirmation in future studies.

Fatty fish intake in mothers during pregnancy and in their children in relation to the development of obesity and overweight in childhood: The prospective ABIS study.

SummaryBackgroundAlthough controversial, lower maternal intake of n‐3 polyunsaturated fatty acid (PUFA) during pregnancy and lower levels of omega‐3 PUFA in serum phospholipids during childhood have been related to obesity. The main source of omega‐3 PUFA is fatty fish in the diet.ObjectivesTo assess the relationship between overweight/obesity and the intake of fatty fish in maternal diet during pregnancy and in children up to 8 years of age.MethodsThe prospective cohort All Children in South‐East Sweden (ABIS) followed babies from birth to 8 years of age. A total of 6749 children at 5 years of age (boys 52.6%) and 3017 children at 8 years (boys 52.3%) participated. A “fatty‐fish index” was constructed on the basis of self‐reports of nutritional habits.ResultsThe prevalence of overweight and obesity in children at 5 years were 12.9% and 4.2%, respectively. At 8 years, 12.2% of the children presented overweight and 2.3% obesity. Girls were more affected than boys by overweight/obesity. A higher fish index during pregnancy was not related to overweight/obesity in the children, whereas a higher fish index in the children during the first years of life was related to obesity at 5 and 8 years of age. This relationship disappeared in a multivariable analysis. Maternal body mass index (BMI), maternal education, maternal smoking during pregnancy, birth weight, and physical activity all remained related to overweight/obesity at both 5 and 8 years of age.ConclusionNo relationships were found between a lower intake of fatty fish in the diet, neither in mothers during pregnancy nor in early childhood, and increased risk of overweight/obesity.

Porcine Hepatic Response to Fumonisin B1 in a Short Exposure Period: Fatty Acid Profile and Clinical Investigations.

Scarce studies have investigated the impact of fumonisin B1 (FB1) on the hepatic tissue fatty acid (FA) profile, and no study is available on piglets. A 10-day in vivo experiment was performed on seven piglets/group: control and FB1-fed animals (diet was contaminated with fungal culture: 20 mg FB1/kg diet). Independent sample t-test was carried out at p < 0.05 as the significance level. Neither growth, nor feed efficiency, was affected. The hepatic phospholipid (PL) fatty acids (FAs) were more susceptible for FB1, while triglyceride (TG) was less responsive. The impact of FB1 on hepatic PL polyunsaturated fatty acids (PUFAs) was more pronounced than on saturated fatty acids. Among all PUFAs, predominant ones in response were docosapentaenoicacid (DPA) (↓), docosahexaenoic DHA (↓) and arachidonic acids (↑). This led to a higher omega-6:omega-3 ratio, whereas a similar finding was noted in TGs. Neither total saturation (SFA) nor total monousaturation (MUFA) were affected by the FB1 administration. The liver showed an increase in malondialdehyde, as well as antioxidant capacity (reduced glutathione and glutathione peroxidase). The plasma enzymatic assessment revealed an increase in alkaline phosphatase (ALP), while alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT) were not influenced. The microscopic sections provided evidence of vacuolar degeneration of the hepatocytes’ cytoplasm, but it was not severe. Furthermore, the lung edema was developed, while the kidney was not affected. In conclusion, regarding FB1-mediated hepatotoxicity in piglets, the potential effect of slight hepatotoxicity did not compromise growth performance, at least at the dose and exposure period applied.