Prostaglandins, leukotrienes, and essential fatty acids最新文献

Here we investigated whether antipsychotic treatment was influenced by three polymorphisms: rs10798059 (BanI) in the phospholipase A2 (PLA2)G4A gene, rs4375 in PLA2G6, and rs1549637 in PLA2G4C. A total of 186 antipsychotic-naïve first-episode psychosis patients or nonadherent chronic psychosis individuals (99 males and 87 females) were genotyped by polymerase chain reaction analysis/restriction fragment length polymorphism. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed patients’ Positive and Negative Syndrome Scale (PANSS) scores, PANSS factors, and metabolic syndrome-related parameters (fasting plasma lipid and glucose levels, and body mass index). We found that PLA2G4A polymorphism influenced changes in PANSS psychopathology, and PLA2G6 polymorphism influenced changes in PANSS psychopathology and metabolic parameters. PLA2G4C polymorphism did not show any impact on PANSS psychopathology or metabolic parameters. The polymorphisms’ effect sizes were estimated as moderate to strong, with contributions ranging from around 6.2–15.7%. Furthermore, the polymorphisms’ effects manifested in a gender-specific manner.

Sickle cell disease (SCD) induces red blood cell sickling, which causes debilitating symptoms including vaso-occlusion and inflammation. We investigated a food enriched with omega-3 fatty acids to determine its effect on certain factors: blood cell membrane fatty acid composition (including anti-inflammatory elements—docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)—and the pro-inflammatory, arachidonic acid (AA)); the inflammation biomarker, C-reactive protein (CRP); and vaso-occlusive crisis (VOC) pain. Ten adults with SCD ingested the food, daily, for 28 days. Evaluated measures included blood cell membrane fatty acid ratios (AA vs omega-3 (DHA+EPA)), CRP (mg/L) levels, and Visual Analogue Scale (VAS) scores (a VOC assessment). The food was well tolerated and led to a statistically significant CRP reduction (39%). However, changes in omega-3 fatty acid ratios and VAS scores were not significant. Overall, while the omega-3-enriched food reduced inflammation, larger, blinded studies are needed to assess its effectiveness on other measures.

The omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic- (EPA), docosahexaenoic- (DHA) and docosapentaenoic acid (DPAn-3) are promising therapeutic options in reducing the severity of anxious and depressive symptoms. However, meta-analyses of randomised controlled trials (RCTs) yield mixed findings. This systematic review and meta-analysis reviewed the evidence and assessed the efficacy of EPA, DHA and DPAn-3 in reducing the severity of anxiety and depression with specific consideration to methodological complications unique to the field e.g., dose and ratio of omega-3 PUFAs and placebo composition. Random-effects meta-analysis of ten RCTs comprising 1426 participants revealed statistically significant reduction in depression severity with EPA-enriched interventions at proportions ≥ 60% of total EPA + DHA (SMD: -0.36; 95% CI: -0.68, -0.05; p = 0.02) (I² = 86%) and EPA doses between ≥ 1 g/day and < 2 g/day (SMD: -0.43; 95% CI: -0.79, -0.07; p = 0.02) (I² = 88%); however, EPA doses ≥ 2 g/day were not associated with significant therapeutic effects (SMD: -0.20; 95% CI: -0.48, 0.07; p = 0.14). Only one study reported significant reduction in anxiety severity with 2.1 g/day EPA (85.6% of total EPA + DHA), therefore meta-analysis was not possible. No trials administering DPAn-3 were identified. Visual examination of the funnel plot revealed asymmetry, suggesting publication bias and heterogeneity amongst the trials. These results support the therapeutic potential of EPA in depression at proportions ≥ 60% of total EPA + DHA and doses ≥ 1 g/day and < 2 g/day. The observed publication bias and heterogeneity amongst the trials reflect the need for more high-quality trials in this area with consideration to the unique nature of omega-3 PUFAs research, to more fully elucidate the therapeutic potential of EPA, DHA and DPAn-3.

Assessment of the nutritional composition of Human Breast Milk (HBM) is important to understand its sufficiency as the sole nutrient source in infants. The present study is aimed to analyze the proximate composition along with total amino acid and fatty acid profile in term and preterm HBM of different socio economic status.

This cross sectional study included, 120 lactating mothers with term or preterm gestation from maternity hospitals located in Hyderabad, Telangana. Nutritional proximate, total amino and fatty acid profiles were estimated in pooled human milk collected from each participant within the first week of postpartum.

The macronutrient composition in term was similar to that of preterm breast milk. The essential amino acid Leucine was significantly high in preterm (8.91 ± 0.18) when compared to term (8.61 ± 0.23). ω-5 fatty acid Myristoleic acid was significantly high in preterm (0.14 ± 0.02) when compared to term (0.11 ± 0.02), whereas ω-6 fatty acids like Docosadienoic Acid and Eicosadienoic acid were found to be significantly high in term when compared to preterm. Further, it was also found that the mono unsaturated and ω-9 fatty acids were significantly high in lower socio economic group, whereas, poly unsaturated and ω -3 and 6 fatty acids were significantly high in upper socio economic group.

The present study concludes that, nutritional composition like essential amino and fatty acids of human milk vary significantly between different gestational age as well as in socio economic groups.

Background

Aspirin and eicosapentaenoic acid (EPA) have colorectal polyp prevention activity, alone and in combination. This study measured levels of plasma and rectal mucosal oxylipins in participants of the seAFOod 2 × 2 factorial, randomised, placebo-controlled trial, who received aspirin 300 mg daily and EPA 2000 mg free fatty acid, alone and in combination, for 12 months.

Methods

Resolvin (Rv) E1, 15-epi-lipoxin (LX) A₄ and respective precursors 18-HEPE and 15-HETE (with chiral separation) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry in plasma taken at baseline, 6 months and 12 months, as well as rectal mucosa obtained at trial exit colonoscopy at 12 months, in 401 trial participants.

Results

Despite detection of S- and R- enantiomers of 18-HEPE and 15-HETE in ng/ml concentrations, RvE1 or 15‑epi-LXA₄ were not detected above a limit of detection of 20 pg/ml in plasma or rectal mucosa, even in individuals randomised to both aspirin and EPA. We have confirmed in a large clinical trial cohort that prolonged (12 months) treatment with EPA is associated with increased plasma 18-HEPE concentrations (median [inter-quartile range] total 18-HEPE 0.51 [0.21–1.95] ng/ml at baseline versus 0.95 [0.46–4.06] ng/ml at 6 months [P<0.0001] in those randomised to EPA alone), which correlate strongly with respective rectal mucosal 18-HEPE levels (r = 0.82; P<0.001), but which do not predict polyp prevention efficacy by EPA or aspirin.

Conclusion

Analysis of seAFOod trial plasma and rectal mucosal samples has not provided evidence of synthesis of the EPA-derived specialised pro-resolving mediator RvE1 or aspirin-trigged lipoxin 15‑epi-LXA₄. We cannot rule out degradation of individual oxylipins during sample collection and storage but readily measurable precursor oxylipins argues against widespread degradation.

Fatty acids (FA) differ in their transfer efficiencies and metabolic partitioning and lactating cows provide a robust model to investigate kinetics of FA transport. The objective was to compare kinetics of n-3 polyunsaturated FA (PUFA) trafficking through plasma and into milk. In the first experiment, ten ruminally cannulated multiparous Holstein cows were used in a crossover design with 7 d periods. Cows were milked at 6 h intervals and abomasal treatments provided a single dose of 80.1 g of α-linolenic acid as free FA (ALA-FFA) or 45.5 g EPA and 32.9 g DHA (LCn3-FFA). Transfer of n-3 PUFA to milk was nearly 50% higher for ALA-FFA than LCn3-FFA (48.2 and 32.7% of the bolus) and fit a bi-exponential model. Rapid transport of n-3 PUFA, assumed to be directly through chylomicrons, was nearly twice as high in ALA-FFA than LCn3-FFA and the subsequent slow transport, assumed to be indirect transfer through tissue recycling, was over 2.5-fold higher in LCn3-FFA than in ALA-FFA. Plasma analysis revealed LCn3-FFA enriched phospholipids and cholesterol esters, which had a slow clearance. In the second experiment, 4 cows received a bolus of a mixture of ALA, EPA, and DHA prepartum while not lactating and around d 10, 55, and 225 of lactation. Transfer of ALA to milk did not differ between stages of lactation, but DHA was lower in early compared to mid and late lactation. In conclusion, dietary ALA is rapidly and efficiently transferred to milk in cows while EPA and DHA are rapidly incorporated into plasma or tissue fractions not available to the mammary gland. This demonstrates clear differences in trafficking and partitioning of n-3 PUFA that ultimately impact tissue and organelle enrichment with implications for effective doses.

Oncostatin M produced by osteal macrophages plays a significant role in fracture healing. Osteoprotegerin (OPG) secreted by osteoblasts, binds to the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) as a decoy receptor and prevents RANKL from binding to RANK, resulting in bone resorption suppression. Interleukin-6 (IL-6) is a pro-inflammatory cytokine and generally regulates bone resorption. However, accumulating evidence suggests that IL-6 plays pivotal roles in bone formation. We previously showed that prostaglandin D₂ (PGD₂) induces OPG synthesis by activating p38 mitogen-activated protein (MAP) kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. Furthermore, we demonstrated that PGD₂ stimulates IL-6 synthesis by activating p38 MAP kinase and p44/p42 MAP kinase in MC3T3-E1 cells. In the present study, we investigated whether oncostatin M affects PGD₂-stimulated OPG and IL-6 synthesis in MC3T3-E1 cells through MAP kinase activation. The osteoblast-like MC3T3-E1 cells and normal human osteoblasts were treated with oncostatin M and subsequently stimulated with PGD₂. Consequently, oncostatin M significantly increased the PGD₂-stimulated OPG and IL-6 release in both cells. Oncostatin M significantly enhanced mRNA expression levels of OPG and IL-6 induced by PGD₂ similarly in both cells. Regarding the signaling mechanism, oncostatin M did not affect the phosphorylation of p38 MAP kinase, SAPK/JNK, and p44/p42 MAP kinase. Our results suggest that oncostatin M upregulates the PGD₂-stimulated OPG and IL-6 synthesis in osteoblasts and therefore affects bone remodeling. However, OPG and IL-6 synthesis are not mediated through p38 MAP kinase, p44/p42 MAP kinase, or SAPK/JNK pathways.

High red blood distribution width (RDW) is associated with decreased red blood cell deformability, and high neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and innate-adaptive immune system imbalance. Both RDW and NLR are predictors of chronic disease risk and mortality. Omega-3 index (O3I) values have previously been shown to be inversely associated with RDW and NLR levels. Our objective was to determine if total plasma long chain omega-3 fatty acids (Omega3%) measured in the UK Biobank cohort were associated with RDW and NLR values. RDW- and NLR- relationships with Omega3% were characterized in 109,191 adults (58.4% female). RDW- and NLR-Omega3% relationships were inversely associated with Omega3% (both p < 0.0001). These cross-sectional associations confirm previous findings that increasing RDW and NLR values are associated with low O3I. The hypothesis that RDW and/or NLR values can be reduced in individuals with less-than optimal long chain omega 3 values need to be tested in randomized controlled intervention trials using EPA and/or DHA.

Purpose

n-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA; C22:6 n3) and eicosapentaenoic acid (EPA; C20:5 n3), are of concern for their health-promoting effects such as anti-inflammatory, but the tissue selectivity for n-3 PUFA (i.e., which tissues and organs are rich in n-3 PUFA) is still not well known. In addition, it is unclear which tissues and organs are more sensitive to n-3 PUFA intervention. These unresolved issues have greatly hindered the exploring of the health benefits of n-3 PUFA.

Methods

Twenty-four 7-week-old male C57BL/6 J mice were assigned to the control, fish oil, DHA, and EPA groups. The last three groups were given a 4-week oral intervention of fatty acids in ethyl ester (400 mg/kg bw). The fatty acid profiles in 27 compartments were determined by gas chromatography.

Results

The proportion of long-chain n-3 PUFA (the total relative percentage of EPA, DPA n3, and DHA) was analyzed. Eight tissues and organs, including the brain (cerebral cortex, hippocampus, hypothalamus) and peripheral organs (tongue, quadriceps, gastrocnemius, kidney, and heart) were determined as being n-3 PUFA-enriched tissues and organs, owing to their high n-3 PUFA levels. The highest n-3 PUFA content was observed in the tongue for the first time. Notably, the content of linoleic acid (LA; C18:2 n6c) in peripheral organs was observed to be relatively high compared with that in the brain. Interestingly, the proportions of EPA in the kidney, heart, quadriceps, gastrocnemius, and tongue increased more markedly after the EPA intervention than after the DHA or fish oil intervention. As expected, the levels of proinflammatory arachidonic acid (AA; C20:4 n6) in the kidney, quadriceps, and tongue were markedly decreased after the three dietary interventions.

Conclusion

Peripheral tissues and organs, including the tongue, quadriceps, gastrocnemius, kidney, and heart, besides the brain, showed obvious tissue selectivity for n-3 PUFA. In the whole body of mice, the tongue exhibits the strongest preference for n-3 PUFA, with the highest proportion of n-3 PUFA. Moreover, these peripheral tissues and organs, especially the kidney, are more sensitive to dietary EPA administration in comparison with the brain.

Recent studies suggest the effects of DHA supplementation on human memory may differ between females and males during infancy, adolescence, and early adulthood, but the underlying mechanisms are not clear. As a result, this study sought to examine the spatial memory and brain lipidomic profiles in female and male adolescent rats with or without a DHA-enriched diet that began perinatally with the supplementation of dams. Spatial learning and memory were examined in adolescent rats using the Morris Water Maze beginning at 6 weeks of age and animals were sacrificed at 7 weeks of age to permit isolation of brain tissue and blood samples. Behavioral testing showed that there was a significant diet x sex interaction for two key measures of spatial memory (distance to zone and time spent in the correct quadrant during the probe test), with female rats benefiting the most from DHA supplementation. Lipidomic analyses suggest levels of arachidonic acid (ARA) and n-6 docosapentaenoic acid (DPA) containing phospholipid species were lower in the hippocampus of DHA supplemented compared with control animals, and principal component analyses revealed a potential dietary treatment effect for hippocampal PUFA. Females fed DHA had slightly more PE P-18:0_22:6 and maintained levels of PE 18:0_20:4 in the hippocampus in contrast with males fed DHA. Understanding how DHA supplementation during the perinatal and adolescent periods changes cognitive function in a sex-specific manner has important implications for determining the dietary requirements of DHA. This study adds to previous work highlighting the importance of DHA for spatial memory and provides evidence that further research needs to consider how DHA supplementation can cause sex-specific changes.