Docosahexaenoic acid, eicosapentaenoic acid, arachidonic acid, and neural tube defects in Tunisian population.

OBJECTIVE: To determine the effect of maternal status in (plasma and red blood cell) folate, vitamin B12, homocysteine, and vitamin D, as well as their interaction with MTHFR (C677T and A1298C) and MTRR A66G polymorphisms, on maternal plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) levels and the risk of neural tube defects (NTDs). METHODS: ARA, EPA, and DHA composition was assessed using capillary gas chromatography. RESULTS: ARA and DHA levels were higher in controls than in case mothers for low plasma folate status. For low red blood cell folate status, DHA levels were higher in controls than in case mothers. For high homocysteine levels, ARA and DHA levels were higher in controls than in case mothers. NTD mothers had lower EPA and DHA levels for low vitamin B12 levels. NTD mothers had lower DHA levels for low vitamin D levels. For low plasma folate status, DHA levels in the MTHFR C677T gene and ARA and EPA levels in MTHFR A1298C gene were different among the three genotypes in case mothers. DHA levels in the MTHFR C677T gene were different among the three genotypes in case mothers for both low and high homocysteine levels. For low vitamin B12 levels, ARA and DHA levels were different among the three genotypes of the MTHFR C677T gene in case mothers. In the MTHFR C677T gene, ARA and DHA levels were different among the three genotypes in case mothers for low vitamin D levels. CONCLUSIONS: More advanced research is required to verify a suitable biochemical parameter status in relation to the genotypes in pregnant women.

Eicosapentaenoic Acid and the Outcomes in Older Patients Undergoing Atrial Fibrillation Ablation.

BACKGROUND: A lower serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio (EPA/AA) level correlates with cardiovascular events. Nevertheless, elevated serum EPA levels increase the risk of new-onset atrial fibrillation (AF) in older patients. The relationship between the EPA/AA and outcomes post-AF ablation remains unclear. This study investigated the impact of the EPA/AA on AF recurrence and cardiovascular events after AF ablation in older patients. METHODS AND RESULTS: This retrospective cohort study examined consecutive patients with AF aged ≥65 years who underwent a first-time AF ablation. We compared the 3-year AF recurrence and 5-year major adverse cardiovascular event (MACE) rates between patients divided into high and low EPA/AA levels defined as above and below the median EPA/AA value before ablation. MACE was defined as heart failure hospitalizations, strokes, coronary artery disease, major bleeding, and cardiovascular death. Among the 673 included patients, the median EPA/AA value was 0.35. Compared with the low EPA/AA group, the high EPA/AA group had a significantly higher cumulative incidence of AF recurrence (39.3% versus 27.6%; log-rank P=0.004) and lower cumulative incidence of MACE (13.8% versus 25.5%, log-rank P=0.021). A high EPA/AA level was determined as an independent predictor of AF recurrence (hazard ratio [HR], 1.75 95% CI, 1.24-2.49; P=0.002) and MACE (HR, 0.60 [95% CI, 0.36-0.99]; P=0.046). CONCLUSIONS: The EPA/AA was associated with AF recurrence and MACE after ablation in patients with AF aged ≥65 years.

Contributing to the management of viral infections through simple immunosensing of the arachidonic acid serum level.

A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid (ARA), a highly significant biological regulator with decisive roles in viral infections. The designed methodology involves a competitive reaction between the target endogenous ARA and a biotin-ARA competitor for the recognition sites of anti-ARA antibodies covalently attached to the surface of carboxylic acid-coated magnetic microbeads (HOOC-MµBs), followed by the enzymatic label of the biotin-ARA residues with streptavidin-horseradish peroxidase (Strep-HRP) conjugate. The resulting bioconjugates were magnetically trapped onto the sensing surface of disposable screen-printed carbon transducers (SPCEs) to monitor the extent of the biorecognition reaction through amperometry. The operational functioning of the exhaustively optimized and characterized immunosensing bioplatform was highly convenient for the quantitative determination of ARA in serum samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-) and respiratory syncytial virus (RSV)-infected individuals in a rapid, affordable, trustful, and sensitive manner.

Inhibiting arachidonic acid generation mitigates aging-induced hyperinsulinemia and insulin resistance in mice.

BACKGROUND: Aging-related type 2 diabetes (T2DM) is characterized by hyperinsulinemia, insulin resistance, and ß-cell dysfunction. However, the underlying molecular mechanisms remain to be unclear. METHODS: We conducted non-targeted metabolomics to compare human serum samples from young adults (YA), elderly adults (EA), and elderly adults with diabetes (EA + DM) of Chinese population. Adult mice and aged mice were intragastrically administered with varespladib every day for two weeks and metabolic characteristics were monitored. Serum levels of arachidonic acid, insulin, and C-peptide, as well as serum activity of secretory phospholipase A2 (sPLA2) were detected in mice. Mouse islet perfusion assays were used to assess insulin secretion ability. Phosphorylated AKT levels were measured to evaluate insulin sensitivities of peripheral tissues in mice. RESULTS: Non-targeted metabolomics analysis of human serum samples revealed differential metabolic signatures among the YA, EA, and EA + DM groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant enhancement of arachidonic acid metabolism and glycerophospholipid metabolism in the EA group compared with the YA group. Further analysis identified two metabolic fluxes that favored the accumulation of arachidonic acid in the elderly. Increased levels of arachidonic acid were also confirmed in aged mice with hyperinsulinemia and insulin resistance, together with subsequent glucose intolerance. Conversely, inhibiting the generation of arachidonic acid with varespladib, an inhibitor of sPLA2, reduced aging-associated diabetes by improving hyperinsulinemia and hepatic insulin resistance in aged mice but not in adult mice. Islet perfusion assays also showed that varespladib treatment suppressed the enhanced insulin secretion observed in aged islets. CONCLUSIONS: Collectively, our findings uncover that arachidonic acid serves as a metabolic hub in Chinese elderly population. Our results also suggest that arachidonic acid plays a fundamental role in regulating ß-cell function during aging and point to a novel therapy for aging-associated diabetes.

Changes in the Fatty Acid Profile in Erythrocytes in High-Level Endurance Runners during a Sports Season.

Fatty acids (FAs) are an essential component of the erythrocyte membrane, and nutrition and physical exercise are two variables that affect their structure and function. The aim of this study was to evaluate the erythrocyte profile in a group of high-level endurance runners, as well as the changes in different FAs, throughout a sports season in relation to the training performed. A total of 21 high-level male endurance runners (23 ± 4 years; height: 1.76 ± 0.05) were evaluated at four different times throughout a sports season. The athletes had at least 5 years of previous experience and participated in national and international competitions. The determination of the different FAs was carried out by gas chromatography. The runners exhibited low concentrations of docosahexaenoic acid (DHA) and omega-3 index (IND ω-3), as well as high values of stearic acid (SA), palmitic acid (PA), and arachidonic acid (AA), compared to the values of reference throughout the study. In conclusion, training modifies the erythrocyte FA profile in high-level endurance runners, reducing the concentrations of polyunsaturated fatty acids (PUFAs) such as DHA and AA and increasing the concentrations of saturated fatty acids (SFAs) such as SA and the PA. High-level endurance runners should pay special attention to the intake of PUFAs ω-3 in their diet or consider supplementation during training periods to avoid deficiency.

Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes.

Neonatal sepsis is a major cause of childhood mortality. Limited diagnostic tools and mechanistic insights have hampered our abilities to develop prophylactic or therapeutic interventions. Biomarkers in human neonatal sepsis have been repeatedly identified as associated with dysregulation of angiopoietin signaling and altered arachidonic acid metabolism. We here provide the mechanistic evidence in support of the relevance for these observations. Angiopoetin-1 (Ang-1), which promotes vascular integrity, was decreased in blood plasma of human and murine septic newborns. In preclinical models, administration of Ang-1 provided prophylactic protection from septic death. Arachidonic acid metabolism appears to be functionally connected to Ang-1 via reactive oxygen species (ROS) with a direct role of nitric oxide (NO). Strengthening this intersection via oral administration of arachidonic acid and/or the NO donor L-arginine provided prophylactic as well as therapeutic protection from septic death while also increasing plasma Ang-1 levels among septic newborns. Our data highlight that targeting angiogenesis-associated pathways with interventions that increase Ang-1 activity directly or indirectly through ROS/eNOS provide promising avenues to prevent and/or treat severe neonatal sepsis.

The prognostic value of platelet aggregation in patients with sepsis.

BACKGROUND: This study aims to investigate the relevance of platelet aggregation markers, specifically arachidonic acid (AA) and adenosine diphosphate (ADP), in relation to the prognosis of sepsis patients. METHODS: A cohort of 40 sepsis patients was included and stratified, based on their 28-day post-treatment prognosis, into two groups: a survival group (n = 31) and a severe sepsis group (n = 9. Then, their various clinical parameters, including patient demographics, platelet counts (PLT), inflammatory markers, and platelet aggregation rates (PAR) induced by AA and ADP between the two groups, were compared. Long-term health implications of sepsis were assessed using the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score, and logistic regression analysis was conducted to evaluate the prognostic significance of PAR in sepsis patients. RESULTS: Patients with severe sepsis exhibited significantly elevated levels of procalcitonin (PCT), platelet adhesion rates, and PAR induced by ADP (P < 0.05), but having lower PLT (P < 0.05), compared to those in the survival group. Logistic regression analysis demonstrated that PAR induced by ADP was a protective factor in predicting prognosis in sepsis patients (P < 0.01). CONCLUSIONS: Activation of platelets in sepsis intensifies inflammatory response. Patients with sepsis whose ADP-induced PAR was < 60% displayed significant impairment in platelet aggregation function, and had higher mortality rate. Monitoring ADP-induced PAR is crucial for management of sepsis.

Omega-3 Status Evaluation in Australian Female Rugby League Athletes: Ad Libitum Fish Oil Provision Results in a Varied Omega-3 Index.

Optimal omega-3 status, influenced by increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is vital for physiological health. This study investigated the impact of ad libitum fish oil supplementation on the omega-3 status of female athletes in a professional rugby league team during a competitive season. Twenty-four (n = 24) athletes participated, and their omega-3 status was assessed using the Omega-3 Index (O3I) and arachidonic acid (AA) to EPA ratio through finger-prick blood samples taken at the start and end of the season. They were given access to a fish oil supplement (PILLAR Performance, Australia) with a recommended daily dose of four capsules per day (2,160 mg EPA and 1,440 mg docosahexaenoic acid). At the beginning of the season, the group mean O3I was 4.77% (95% confidence interval [CI: 4.50, 5.04]) and the AA to EPA ratio was 14.89 (95% CI [13.22, 16.55]). None of the athletes had an O3I exceeding 8%. By the season's end, the O3I was a significantly increased to 7.28% (95% CI [6.64, 7.93], p < .0001) and AA to EPA ratio significantly decreased to a mean of 6.67 (95% CI [5.02, 8.31], p < .0001), driven primarily by the significant increase in EPA of +1.14% (95% CI [0.77, 1.51], p < .0001). However, these changes were varied between the athletes and most likely due to compliance. This study has demonstrated that using the objective O3I feedback scale is possible with elite female rugby athletes, but individual strategies will be required to achieve daily intake targets of EPA + DHA.

Arachidonic acid and docosahexaenoic acid levels correlate with the inflammation proteome in extremely preterm infants.

BACKGROUND & AIM: Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown positive effects on inflammation-related morbidities, but the molecular mechanisms underlying these effects are not fully elucidated. This study aimed to determine associations between DHA, AA, and inflammation-related proteins during the neonatal period in extremely preterm infants. METHODS: A retrospective exploratory study of infants (n = 183) born below 28 weeks gestation from the Mega Donna Mega trial, a randomized multicenter trial designed to study the effect of DHA and AA on retinopathy of prematurity. Serial serum samples were collected after birth until postnatal day 100 (median 7 samples per infant) and analyzed for phospholipid fatty acids and proteins using targeted proteomics covering 538 proteins. Associations over time between LCPUFAs and proteins were explored using mixed effect modeling with splines, including an interaction term for time, and adjusted for gestational age, sex, and center. RESULTS: On postnatal day one, 55 proteins correlated with DHA levels and 10 proteins with AA levels. Five proteins were related to both fatty acids, all with a positive correlation. Over the first 100 days after birth, we identified 57 proteins to be associated with DHA and/or AA. Of these proteins, 41 (72%) related to inflammation. Thirty-eight proteins were associated with both fatty acids and the overall direction of association did not differ between DHA and AA, indicating that both LCPUFAs similarly contribute to up- and down-regulation of the preterm neonate inflammatory proteome. Primary examples of this were the inflammation-modulating cytokines IL-6 and CCL7, both being negatively related to levels of DHA and AA in the postnatal period. CONCLUSIONS: This study supports postnatal non-antagonistic and potentially synergistic effects of DHA and AA on the inflammation proteome in preterm infants, indicating that supplementation with both fatty acids may contribute to limiting the disease burden in this vulnerable population. CLINICAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03201588).

Enteral supplementation with arachidonic and docosahexaenoic acid and pulmonary outcome in extremely preterm infants.

Enteral supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) in extremely preterm infants has shown beneficial effects on retinopathy of prematurity and pulmonary outcome whereas exclusive DHA supplementation has been associated with increased pulmonary morbidity. This secondary analysis evaluates pulmonary outcome in 204 extremely preterm infants, randomized to receive AA (100 mg/kg/day) and DHA (50 mg/kg/day) enterally from birth until term age or standard care. Pulmonary morbidity was primarily assessed based on severity of bronchopulmonary dysplasia (BPD). Serum levels of AA and DHA during the first 28 days were analysed in relation to BPD. Supplementation with AA:DHA was not associated with increased BPD severity, adjusted OR 1.48 (95 % CI 0.85-2.61), nor with increased need for respiratory support at post menstrual age 36 weeks or duration of oxygen supplementation. Every 1 % increase in AA was associated with a reduction of BPD severity, adjusted OR 0.73 (95 % CI 0.58-0.92). In conclusion, in this study, with limited statistical power, enteral supplementation with AA:DHA was not associated with an increased risk of pulmonary morbidity, but higher levels of AA were associated with less severe BPD. Whether AA or the combination of AA and DHA have beneficial roles in the immature lung needs further research.

Plasma phospholipid arachidonic acid in relation to non-alcoholic fatty liver disease: Mendelian randomization study.

OBJECTIVES: The role of plasma phospholipid arachidonic acid (AA) in the development of non-alcoholic fatty liver disease (NALFD), cirrhosis, and liver cancer remains unclear. This study aimed to determine the causality of the associations of plasma phospholipid AA with NALFD, cirrhosis, and liver cancer using Mendelian randomization analysis. METHODS: Nine independent single-nucleotide polymorphisms associated with plasma phospholipid AA at the genome-wide significance were used as instrumental variables. Summary-level data for three outcomes were obtained from 1) a genome-wide association study for NAFLD, 2) the UK Biobank study, and 3) the FinnGen study. The sensitivity analysis excluding the pleiotropic variant rs174547 in the FADS1 gene was performed. Estimates from different sources were combined using the fixed-effects meta-analysis method. RESULTS: Per standard deviation increase in AA levels, the combined odds ratio was 1.06 (95% confidence interval, 1.02-1.11; P = 0.008) for NAFLD, 1.05 (95% confidence interval, 1.01-1.09; P = 0.009) for cirrhosis, and 0.99 (95% confidence interval, 0.94-1.05; P = 0.765) for liver cancer. The associations remained stable in the sensitivity analysis excluding rs174547. CONCLUSIONS: This study suggests potential causal associations of high levels of plasma phospholipid AA with the risk of NAFLD and cirrhosis.

Causal analysis of serum polyunsaturated fatty acids with juvenile idiopathic arthritis and ocular comorbidity.

BACKGROUND & OBJECTIVE: To investigate the causal effects of plasma Polyunsaturated fatty acids (PUFAs) on the risk of juvenile idiopathic arthritis (JIA) and ocular comorbidity through Mendelian randomization (MR) analysis. METHODS: Genetic variants (formerly single nucleotide polymorphisms, SNPs) that are strongly associated with PUFAs levels (P < 5×10-8) were selected as instrumental variables. Summary-level MR was performed with outcome estimates for JIA (n = 31,142) and JIA associated iridocyclitis (n = 94,197). The inverse variance-weighted (IVW) method was employed as the main approach to combine the estimation for each SNP. Two set of models with summary statistics were conducted and multiple sensitivity analyses were applied for testing of pleiotropic bias. RESULTS: In model 1, genetically predicted n-6 PUFAs linoleic acid (LA) and arachidonic acid (AA) were associated with lower and higher risk of JIA associated iridocyclitis using IVW (ORLA = 0.940, 95% CI: 0.895-0.988, P = 0.015; ORAA = 1.053, 95% CI: 1.007-1.101, P = 0.024). No such association was observed between each plasma PUFAs and JIA susceptibility (P > 0.05). In further MR analysis, results from model 2 also showed a consistent trend. Besides, multiple sensitivity analyses revealed that there was no obvious evidence for unknown pleiotropy (P > 0.05). CONCLUSIONS: Our MR study provides genetic evidence on the possible causality that plasma LA level might protect against JIA associated iridocyclitis, whereas AA was responsible for opposite effect.

Single nucleotide polymorphism of fatty acid desaturase gene and breast cancer risk in estrogen receptor subtype.

BACKGROUND: Breast cancer (BC) is the most common cancer of women and the second most common cancer overall globally. Data suggest that the plasma concentration of omega fatty acids (n-3 and n-6) and the impact of the genetic variant are associated with diet-related inflammatory disease, BC. This study was aimed to find an association between genetic variant rs174537 of fatty acid desaturase gene 1(FADS 1) and breast cancer estrogen receptor subtype. METHODOLOGY: Hundred and two blood samples from women were quantified for fatty acids by gas chromatography. SNP rs 174537(G > T) showed maximum variability and the strongest genetic determinant in the Genome-wide association study were genotyped using Sanger sequencing. RESULTS: The highest tertile of ALA showed a significantly reduced risk of BC compared to the lowest tertile (OR = 0.2, 95 %CL = 0.1-1.14, P = 0.03). Median values of ALA were higher in GT/TT genotype in ER +ve molecular subtype (P = 0.03) and DPA was higher in GG genotype of ER-ve molecular subtype (P = 0.037). When both the groups were put together the highest tertile of GG tertile showed significantly reduced risk of BC compared with the other lowest tertiles of GG and GT/TT genotypes (OR, 95% CL = 0.45(0.2-0.9). CONCLUSION: The high levels of arachidonic acid and low levels of n-3 fatty acids result in a pro-inflammatory milieu and that these pro-inflammatory effects might contribute to BC. We conclude that the individuals with genetically determined lower activity of FADS1(minor allele T) will derive greater advantage from n-3 FAs than those with higher FADS1 activity (G allele) and reduce the BC risk.

Does the Degree of Platelet Adenosine Diphosphate and Arachidonic Acid Receptor Inhibition Correlate With the Severity of Injury in Non-Brain-Injured Trauma Patients?

BACKGROUND: Direct correlations between platelet adenosine diphosphate (ADP) and arachidonic acid (AA) receptor inhibition have been described in the traumatic brain injury (TBI) population. Our goal was to evaluate the percent inhibition of ADP receptor inhibition (ADPri) and AA receptor inhibition (AAri) receptors in non-TBI patients and correlate injury severity and outcomes. METHODS: We performed a retrospective review of non-TBI patients admitted to our trauma center, who received thromboelastography with platelet mapping prior to blood transfusion. Exclusion criteria included patients younger than 18 years, current antiplatelet therapy, or history of renal failure. Univariate descriptive statistics and bivariate comparisons were performed on patient demographic and outcomes. Multivariable linear regression models were constructed to quantify any association between ADPri and AAri with injury outcomes. High ADP inhibition was defined >20% and high AA inhibition >7%. RESULTS: 117 patients met inclusion criteria. Mean age was 53 years with 61% male. Mean ADPri was 64% and AAri 42%. On bivariate analysis, no statistically significant differences with respect to injury severity measures or outcomes were identified. On multivariable linear regression, AAri was associated with longer hospital length of stay. DISCUSSION: There was a high degree of platelet dysfunction in this cohort of severely injured patients without TBI. Despite this, the only correlation identified between injury severity and outcomes was AAri correlating with hospital length of stay. Irrespective of injury severity or outcomes, these patients' results were far from reported "normal" values. Further, research is needed to determine the significance and clinical implications of thromboelastography with platelet mapping use in trauma care.

A Protective Role for Arachidonic Acid Metabolites against Advanced Colorectal Adenoma in a Phase III Trial of Selenium.

Oxylipins derived from arachidonic acid (ARA) have been implicated in the development of colorectal adenomas and colorectal cancer. The primary purpose of this work was to determine the relationship between plasma levels of oxylipins and colorectal adenoma characteristics at study entry, as well as with the development of a new adenoma during follow-up within a Phase III adenoma prevention clinical trial with selenium (Sel). Secondarily, we sought to determine whether the selenium intervention influenced plasma oxylipin levels. Four oxylipins were quantified in stored plasma samples from a subset of Sel study subjects (n = 256) at baseline and at 12-months. There were significantly lower odds of an advanced adenoma at baseline with higher prostaglandin E2 (PGE2), with an OR (95% CI) of 0.55 (0.33-0.92), and with 5-hydroxyeicosatetraenoic acid (5-HETE) ((0.53 (0.33-0.94)); and of a large adenoma with higher PGE2 ((0.52 (0.31-0.87)). In contrast, no associations were observed between any oxylipin and the development of a new adenoma during follow-up. Selenium supplementation was associated with a significantly smaller increase in 5-HETE after 12 months compared to the placebo, though no other results were statistically significant. The ARA-derived oxylipins may have a role in the progression of non-advanced adenoma to advanced, but not with the development of a new adenoma.

Serum arachidonic acid levels is a predictor of poor functional outcome in acute intracerebral hemorrhage.

BACKGROUND AND AIMS: Correlations between serum levels of polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA) and dihomogammalinolenic acid (DHLA) and outcomes following cardiovascular disease have been reported. This study aimed to investigate the relationship between serum levels of PUFAs (including AA) and functional outcomes among intracerebral hemorrhage (ICH) patients. METHODS: From November 2012 to July 2020, ICH patients within 24 h from onset were enrolled. Patients were divided into a good functional outcome group (modified Rankin Scale [mRS] score at 3 months, 0-3) and a poor functional outcome group (mRS score at 3 months, 4-6). We compared baseline variables between groups. RESULTS: Participants comprised 133 patients (mean age, 60 years), with 106 patients (80%) in the good functional outcome group and 27 patients (20%) in the poor functional outcome group. Higher National Institutes of Health Stroke Scale (NIHSS) score and larger hematoma on admission were more frequent in the poor functional outcome group (median NIHSS score 6 vs. 14, p < 0.001; median hematoma volume, 7.5 ml vs. 13.5 ml, p = 0.07). In terms of serum PUFA levels, only median serum AA level was significantly lower in the poor functional outcome group (212 µg/ml vs. 179 µg/ml, p = 0.002). Multivariate logistic regression analysis showed lower serum AA level was independently associated with poor functional outcome (odds ratio 0.986, 95% confidence interval 0.976-0.996, p = 0.009). CONCLUSION: Lower serum AA level was associated with poor functional outcome in ICH patients. AA may represent an important biomarker of severity among ICH patients.

Effect of n-3 long-chain polyunsaturated fatty acid intake on the eicosanoid profile in individuals with obesity and overweight: a systematic review and meta-analysis of clinical trials.

Dietary n-3 polyunsaturated fatty acids (PUFAs) present beneficial effects on counteracting inflammation status, displaying a critical anti-inflammatory role and maintaining physiological homeostasis in obesity. The primary objective of this systematic review was to evaluate the effect of n-3 PUFAs intake on the eicosanoid profile of people with obesity and overweight. The search strategy on Embase, Scopus, PubMed, Web of Science, Cochrane Library, Google Scholar and ProQuest was undertaken until November 2019 and updated January 2021. The effect size of n-3 PUFAs on prostaglandins was estimated by Glass's, type 1 in a random-effect model for the meta-analysis. Seven clinical trials met the eligible criteria and a total of 610 subjects were included in this systematic review, and four of seven studies were included in meta-analysis. The intake of n-3 PUFAs promoted an overall reduction in serum pro-inflammatory eicosanoids. Additionally, n-3 PUFAs intake significantly decreased the arachidonic acid COX-derived PG eicosanoid group levels (Glass's Δ -0⋅35; CI -0⋅62, -0⋅07, I 2 31⋅48). Subgroup analyses showed a higher effect on periods up to 8 weeks (Glass's Δ -0⋅51; CI -0⋅76, -0⋅27) and doses higher than 0⋅5 g of n-3 PUFAs (Glass's Δ -0⋅46; CI -0⋅72, -0⋅27). Dietary n-3 PUFAs intake contributes to reduce pro-inflammatory eicosanoids of people with obesity and overweight. Subgroup's analysis showed that n-3 PUFAs can reduce the overall arachidonic acid COX-derived PG when adequate dose and period are matched.

Gestational diabetes mellitus decreased umbilical cord blood polyunsaturated fatty acids: a meta-analysis of observational studies.

BACKGROUND: Polyunsaturated fatty acid (PUFA) is important for the development of the fetal brain, and the retina. Gestational diabetes mellitus (GDM) may influence maternal and fetal fatty acid metabolism, in turn affecting fetal growth and development. In several studies, maternal and fetal PUFA metabolic differences have been reported between mothers with and without GDM, but not in other studies. Thus, the aim of this meta-analysis (registration number: CRD42020220448) was to compare levels of linoleic acid (LA), α-linolenic acid (ALA), arachidonic acid (AA), docosahexaenoic acid (DHA), and total n-3 and n-6 PUFA between mothers with and without GMD and their fetuses. METHODS: We performed a meta-analysis of observational studies on maternal and fetal fatty acid metabolism, published until May 2021. In addition, we performed subgroup analysis depending on the analyzed tissues (plasma/serum, erythrocyte membrane, or placenta) and the expression modes of fatty acids (concentration or percentage). RESULTS: We included 24 observational studies involving 4335 maternal datasets and 12 studies involving 1675 fetal datasets in the meta-analysis. Levels of AA, DHA, and n-6 and n-3 PUFA were lower in the cord blood of mothers with GDM than in controls (P  <  0.05). Compared to that in controls, in erythrocyte membranes, the percentages of AA, DHA, and n-6 and n-3 PUFA in total fatty acid were lower in mothers with GDM (P  <  0.05), but in plasma/serum, the percentages of AA, DHA, and n-6 PUFA in total fatty acid were higher in mothers with GDM (P  <  0.05). CONCLUSIONS: GDM appears to influence the transfer of PUFAs from mothers to fetuses. The percentage of PUFAs in maternal plasma/serum was higher, and that in erythrocyte membranes was lower in mothers with GDM compared to those with normal glucose tolerance.

Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease.

BACKGROUND: Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors. RESULT: We systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune function and activity are deeply measured and whose genetics are profiled. Our data reveal that several major metabolic pathways, including the alanine/glutamate pathway and the arachidonic acid pathway, have a strong impact on cytokine production in response to ex vivo stimulation. We also examine the genetic regulation of metabolites associated with immune phenotypes through genome-wide association analysis and identify 29 significant loci, including eight novel independent loci. Of these, one locus (rs174584-FADS2) associated with arachidonic acid metabolism is causally associated with Crohn's disease, suggesting it is a potential therapeutic target. CONCLUSION: This study provides a comprehensive map of the integration between the blood metabolome and immune phenotypes, reveals novel genetic factors that regulate blood metabolite concentrations, and proposes an integrative approach for identifying new disease treatment targets.