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Oxylipins are a group of bioactive fatty acid metabolites generated via enzymatic oxygenation. They are notably involved in inflammation, pain, vascular tone, hemostasis, thrombosis, immunity, and coagulation. Oxylipins have become the focus of therapeutic intervention since they are implicated in many conditions, such as nonalcoholic fatty liver disease, cardiovascular disease, and aging. The liver plays a crucial role in lipid metabolism and distribution throughout the organism. Long-term exposure to pesticides is suspected to contribute to hepatic carcinogenesis via notable disruption of lipid metabolism. Prometryn is a methylthio-s-triazine herbicide used to control the growth of annual broadleaf and grass weeds in many cultivated plants. The amounts of prometryn documented in the environment, mainly waters, soil and plants used for human and domestic consumption are significantly high. Previous research revealed that prometryn decreased liver development during zebrafish embryogenesis. To understand the mechanisms by which prometryn could induce hepatotoxicity, the effect of prometryn (185 mg/kg every 48 h for seven days) was investigated on hepatic and plasma oxylipin levels in mice. Using an unbiased LC-MS/MS-based lipidomics approach, prometryn was found to alter oxylipins metabolites that are mainly derived from cytochrome P450 (CYP) and lipoxygenase (LOX) in both mice liver and plasma. Lipidomic analysis revealed that the hepatotoxic effects of prometryn are associated with increased epoxide hydrolase (EH) products, increased sEH and mEH enzymatic activities, and induction of oxidative stress. Furthermore, 9-HODE and 13-HODE levels were significantly increased in prometryn treated mice liver, suggesting increased levels of oxidation products. Together, these results support that sEH may be an important component of pesticide-induced liver toxicity.

Evidence supports associations between polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and psychosis. However, polyunsaturated fatty acid trajectories in the general population have not been characterized, and associations with psychosis spectrum outcomes in early adulthood are unknown. Plasma omega-6 to omega-3 ratio and DHA (expressed as percentage of total fatty acids) were measured by nuclear magnetic spectroscopy at 7, 15, 17, and 24 years of age in participants of ALSPAC (Avon Longitudinal Study of Parents and Children). Curvilinear growth mixture modeling evaluated body mass index–adjusted trajectories of both measures. Outcomes were assessed at 24 years. Psychotic experiences (PEs), at-risk mental state status, psychotic disorder, and number of PEs were assessed using the Psychosis-Like Symptoms interview (n = 3635; 2247 [61.8%] female). Negative symptoms score was measured using the Community Assessment of Psychic Experiences (n = 3484; 2161 [62.0%] female). Associations were adjusted for sex, ethnicity, parental social class, and cumulative smoking and alcohol use. Relative to stable average, the persistently high omega-6 to omega-3 ratio trajectory was associated with increased odds of PEs and psychotic disorder, but attenuated on adjustment for covariates (PEs adjusted odds ratio [aOR] = 1.63, 95% CI = 0.92-2.89; psychotic disorder aOR = 1.69, 95% CI = 0.71-4.07). This was also the case for persistently low DHA (PEs aOR = 1.42, 95% CI = 0.84-2.37; psychotic disorder aOR = 1.14, 95% CI = 0.49-2.67). Following adjustment, persistently high omega-6 to omega-3 ratio was associated with increased number of PEs (β = 0.41, 95% CI = 0.05-0.78) and negative symptoms score (β = 0.43, 95% CI = 0.14-0.72), as was persistently low DHA (number of PEs β = 0.45, 95% CI = 0.14-0.76; negative symptoms β = 0.35, 95% CI = 0.12-0.58). Optimization of polyunsaturated fatty acid status during development warrants further investigation in relation to psychotic symptoms in early adulthood. [ABSTRACT FROM AUTHOR]

Resolvin D2 (RvD2), an endogenous lipid mediator derived from docosahexaenoic acid, has been demonstrated to have analgesic effects. However, little is known about the mechanism underlying RvD2 in pain relief. Herein, we demonstrate that RvD2 targeted the P2X3 receptor as an analgesic. The electrophysiological activity of P2X3 receptors was suppressed by RvD2 in rat dorsal root ganglia (DRG) neurons. RvD2 pre‐application dose‐dependently decreased α,β‐methylene‐ATP (α,β‐meATP)‐induced inward currents. RvD2 remarkably decreased the maximum response to α,β‐meATP, without influencing the affinity of P2X3 receptors. RvD2 also voltage‐independently suppressed ATP currents. An antagonist of the G protein receptor 18 (GPR18), O‐1918, prevented the RvD2‐induced suppression of ATP currents. Additionally, intracellular dialysis of the Gαi/o‐protein antagonist pertussis toxin (PTX), the PKA antagonist H89, or the cAMP analog 8‐Br‐cAMP also blocked the RvD2‐induced suppression. Furthermore, α,β‐meATP‐triggered depolarization of membrane potential along with the action potential bursts in DRG neurons were inhibited by RvD2. Lastly, RvD2 attenuated spontaneous nociceptive behaviors as well as mechanical allodynia produced by α,β‐meATP in rats via the activation of the peripheral GPR18. These findings indicated that RvD2 inhibited P2X3 receptors in rat primary sensory neurons through GPR18, PTX‐sensitive Gαi/o‐proteins, and intracellular cAMP/PKA signaling, revealing a novel mechanism that underlies its analgesic effects by targeting P2X3 receptors. [ABSTRACT FROM AUTHOR]

Societal Impact Statement: New sources of essential and other nutritionally and/or pharmacologically important fatty acids for human use can be discovered through bioprospecting. Demonstrating how fatty acids in plants and algae are distributed across a phylogeny is a critical first step in this process. Here, new sources of essential omega‐3 fatty acids that are critically important to human health were identified, such as green and Chromista algae, bryophytes and some angiosperm families. The identification of certain taxa that are high in critical fatty acids is important for developing new sources of these healthful compounds. Summary: Essential fatty acids (EFA) including long‐chain omega‐3 and omega‐6 EFA are key nutrients that broadly support the health of individuals and the ecosystems they inhabit. Production of these EFA is critical to global nutritional security, and therefore, it is imperative to assess the distribution patterns of FA in plants to bioprospect new resources that do not threaten biodiversity.We used a meta‐analytic approach (phylogenetic signal analysis), which incorporated a wide variety of taxa to map FA profiles including both presence and abundance of specific FA and EFA onto a plant phylogeny including algae, bryophytes, pteridophytes, gymnosperms and angiosperms.Our phylogenetic signal analysis revealed that presence/absence of most FA of interest were randomly or ubiquitously distributed, while FA content was significantly clustered in specific clades for most key FA (including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and nervonic acid). Both green and Chromista algae displayed relatively high proportions of EPA and DHA, while green algae contained higher proportional amounts of stearidonic acid (SDA). Further, signal analysis revealed high proportional content of gamma‐linoleic acid (GLA) in bryophytes and some angiosperm families, suggesting potential sources for bioprospecting GLA.This analysis provides a crucial foundation for understanding the influence of phylogenetic relationships in the relative proportions of key FA in plants and algae across a diverse phylogeny. Furthermore, in demonstrating how fatty acids in plants and algae are distributed across a phylogeny, we provide a critical first step in bioprospecting for new sources of essential and other nutritionally‐ and/or pharmacologically important fatty acids for human use. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study aimed to elucidate the mechanism of oleuropein (OLE) ameliorates non‐alcoholic fatty liver disease (NAFLD) and its underlying mechanisms. RESULTS: Male C57BL/6J mice were fed either a low‐fat diet (LFD), a high‐fat diet (HFD), or a HFD supplemented with 0.03% (w/w) OLE for 16 weeks. OLE supplementation decreased body weight and liver weight, improved serum lipid profiles, and ameliorated HFD‐induced hepatic dysfunction. Liver metabolomics analysis revealed that OLE increased the levels of nicotinamide, tauroursodeoxycholic acid, taurine, and docosahexaenoic acid, which were beneficial for lipid homeostasis and inflammation regulation. OLE exerted its protective effects by activating peroxisome proliferator‐activated receptor alpha (PPARα), a key transcription factor that regulates fibroblast growth factor 21 (FGF21) expression and modulates lipid oxidation, lipogenesis and inflammation pathways. Importantly, OLE supplementation did not significantly affect body weight or liver weight in PPARα knockout (PPARα KO) mice, indicating that PPARα is essential for OLE‐mediated NAFLD prevention. CONCLUSION: Our results suggest that OLE alleviates NAFLD in mice by activating PPARα and modulating liver metabolites. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Polyunsaturated fatty acids (PUFA) are vital molecules in the pharmaceutical, medical, and nutritional industries. Exploration of bacterial strains capable of producing significant amounts of PUFAs offers a promising avenue for biotechnological applications and industrial-scale production. However, an extensive screening of several samples from diverse sources is highly needed to identify a potential strain. The present study provides the results of the evaluation of 15 different screening methodologies (including changes in existing protocols in terms of reagent concentration, incubation temperature and time) for identifying PUFA-producing bacteria in comparison to the gold standard method (Gas chromatography-mass spectrometry), for the first time. The results determined the most effective techniques for each critical PUFA, leading to an optimized screening process that saves time and resources. The H2O2 plate assay using 0.5% or 1% H2O2 for 72 & 96 h of incubation at 15 °C consistently outperformed others for finding bacteria containing total nutritionally important long chain-PUFA (LC-PUFA), linoleic acid, and arachidonic acid. Whereas the 2,3,5-triphenyl tetrazolium chloride broth assay at 10–15 °C was the most effective and semiquantitative screening methodology for eicosapentaenoic acid (EPA) and alpha-linolenic acid-containing bacteria. Apart from the methodological perspectives, the study also revealed certain potential strains to be targeted in the ongoing research on PUFA-containing bacteria. Further, the manuscript forms the first report on the presence of docosahexaenoic acid (DHA) in Shewanella decolorationis, EPA in Psychrobacter maritimus and Micrococcus aloeverae, and both EPA and DHA in Arthrobacter rhombi. Altogether, the paper generates several thought-provoking insights on the methodological perspectives and identifies potential PUFA-containing bacteria with practical applications in future bacteria-based PUFA research.Key points: ¬ Comparative analysis of different screening tests with GC-MS results identified the best methodology for the bacteria containing each essential PUFA. ¬ The results showed the potential bacterial strains for future research on bacterial PUFA production. ¬ 0.5% or 1% H2O2 plate assay with incubation at 15 °C for 72–96 h was the best screening test for LC-PUFAs, LA, and ARA-containing bacteria. ¬ TTC broth assay with incubation at 10–15 °C was graded as the best screening test for EPA and ALA-containing bacteria. [ABSTRACT FROM AUTHOR]

Maternal nutrition was recognized as a significant part of brain growth and maturation in most mammalian species. Timely intervention with suitable nutraceuticals would provide long-term health benefits. We aim to unravel the molecular mechanisms of perinatal undernutrition-induced impairments in cognition and synaptic plasticity, employing animal model based on dietary nutraceutical supplementation. We treated undernourished dams at their gestational, lactational, and at both the time point with Astaxanthin (AsX) and Docosahexaenoic acid (DHA), and their pups were used as experimental animals. We evaluated the cognitive function by subjecting the pups to behavioral tests in their adult life. In addition, we assessed the expression of genes in the hippocampus related to cognitive function and synaptic plasticity. Our results showed downregulation of Brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT-3), cAMP response-element-binding protein (CREB), and uncoupling protein-2 (UCP2) gene expression in pups born to undernourished dams in their adult life, which AsX and DHA modulated. Maternal AsX and DHA supplementation ameliorated the undernutrition-induced learning impairment in novel object recognition (NOR) tests and partially baited radial arm maze (RAM) tasks in offspring's. The expressions of Synapsin-1 and PSD-95 decreased in perinatally undernourished groups compared to control and AsX-DHA treated groups at CA1, CA2, CA3, and DG. AsX and DHA supplementation upregulated BDNF, NT-3, CREB, and UCP2 gene expressions in perinatally undernourished rats, which are involved in intracellular signaling cascades like Ras, PI3K, and PLC. The results of our study give new insights into neuronal differentiation, survival, and plasticity, indicating that the perinatal period is the critical time for reversing maternal undernutrition-induced cognitive impairment in offspring's. [ABSTRACT FROM AUTHOR]

AbstractDocosahexaenoic acid ethyl ester has an important role in the prevention of the neuropsychiatric and neurodegenerative diseases. Its extraction from fish such as the stingray as anoil creates a pharmaceutical formulation. Therefore it is essential to develop fast molecular recognition methods able to perform both qualitative and quantitative determination of docosahexaenoic in stingray meat and liver. A miniplatform incorporating a 3D stochastic microsensor was designed and validated for the molecular recognition of docosahexaenoic acid ethyl ester. The design of the microsensor was based on the modification of a graphene decorated with nitrogen and boron paste (NB-graphene paste) with 10−3mol L−1 alpha-cyclodextrin. A wide linear concentration range (5.0 × 10−14 − 5.0 × 10−7 g mL−1) and a low limit of quantitation (5.0 × 10−14 g mL−1) were obtained. High recovery values were determined when the miniplatform was used for the assay of docosahexaenoic acid ethyl ester from stingray liver and meat with recoveries higher than 99.20%. The relative standard deviation values were less than 0.05 (N = 10). [ABSTRACT FROM AUTHOR]

(1) Background: Plasmalogens are vinyl ether-type glycerophospholipids that are characteristically distributed in neural tissues and are significantly reduced in the brains of individuals with dementia compared to those in healthy subjects, suggesting a link between plasmalogen deficiency and cognitive decline. Hen eggs are expected to be a potential source of dietary plasmalogens, but the details remain unclear. (2) Methods: We evaluated the fresh weight, dry weight, total lipid, neutral lipids, glycolipids, and phospholipids in the egg yolk and egg white of hen egg. Then, the molecular species of plasmalogens were quantified using HPLC-ESI-MS/MS. (3) Results: In egg yolk, the total plasmalogen content was 1292.1 µg/100 g fresh weight and predominantly ethanolamine plasmalogens (PE-Pls), specifically 18:0/22:6-PE-Pls, which made up 75.6 wt% of the total plasmalogen. In egg white, the plasmalogen content was 31.4 µg/100 g fresh weight and predominantly PE-Pls, specifically 18:0/20:4-PE-Pls, which made up 49.6 wt% of the total plasmalogen. (4) Conclusions: Plasmalogens were found to be more enriched in egg yolk than in egg white. It was found that humans are likely to ingest almost 0.3 mg of total plasmalogens from one hen egg. These findings highlight the importance of plasmalogens in the daily diet, and it is recommended to explore the impact of long-term dietary plasmalogen intake to assess its effect on human health. This provides a viewpoint for the development of new food products. [ABSTRACT FROM AUTHOR]

Background/Objectives: The multifactorial nature of atherosclerotic cardiovascular disease (ASCVD) implicates genetic, environmental, and dietary habits. Antioxidants found in foods have garnered attention for their potential role in mitigating ASCVD risk by combating oxidative stress. This study seeks to confirm the findings of previous research through a large-scale cross-sectional analysis performed in a unique population with Korea National Health and Nutrition Examination Survey data to explore the association between the composite dietary antioxidant index (CDAI) and ASCVD prevalence among middle- and old-aged individuals in South Korea. Methods: This study includes data from 2016 to 2021. The CDAI was calculated based on nutrition intake, including zinc, beta-carotene, vitamin A, vitamin C, vitamin E, and docosahexaenoic acid. This cross-sectional analysis explored the relationship between the CDAI and ASCVD after adjusting for relevant covariates. Logistic regression models were employed, and subgroup analyses by sex were conducted to discern sex-specific effects. Results: A total of 19,818 individuals were analyzed, with 7.0% of them diagnosed with ASCVD. CDAI distribution and antioxidant analyses revealed higher CDAI levels in non-ASCVD individuals. Standardized antioxidant values increased across CDAI quartiles. Initially, a significant association (odds ratio [95% confidence interval]: 0.96 [0.94–0.99]) was found between the CDAI and ASCVD, which was attenuated after adjusting for covariates (1.0 [0.98–1.02]). Subgroup analyses by sex showed nuanced associations, with the CDAI potentially reducing the risk of ASCVD in men (0.71 [0.53–0.94]) while increasing it in women (1.4 [1.01–1.95]). Conclusions: This study provides valuable insights into the association between dietary antioxidant intake and the risk of ASCVD, highlighting sex-specific differences. [ABSTRACT FROM AUTHOR]

Astaxanthin (Ax) determines the flesh redness of a salmonid fish which is the most desirable quality indicator by consumers. Fish cannot synthesize Ax de novo, therefore, the only way to increase flesh redness is to increase dietary input or improve the absorption and retention rate of dietary Ax. As a hydrophobic carotenoid, the absorption of Ax can be modulated by other lipid molecules in the diet. The present study explored the effect of three lipids, cholesterol (CH), phytosterol (PS), and docosahexaenoic acid (DHA) on Ax absorption, transport, and retention in rainbow trout. Dietary CH significantly improved Ax absorption by elevating plasma Ax levels (p < 0.05); however, it had no effect on the whole body Ax or flesh color. Dietary PS appears to inhibit Ax absorption since fish had significantly (p < 0.05) reduced whole body Ax. Dietary DHA appeared to have no effect on Ax absorption or retention. By comparing intestinal transcriptomes, a low density lipoprotein receptor (ldlr) gene was significantly downregulated in fish fed the CH diet as compared to the control diet. Since LDLR protein plays a major role in plasma lipoprotein turnover, we hypothesized that the inhibition of ldlr gene by high dietary CH resulted in higher retention of plasma Ax. The elevation of plasma Ax was not reflected in higher flesh coloration, which suggested other limiting factors governing Ax retention in the muscle. On the other hand, the transcriptomic and proteomic analyses found no changes of genes or proteins involved in Ax absorption, transport, or excretion in fish fed PS or DHA diets as compared to the control diet. In conclusion, this study has suggested that CH promotes Ax absorption by regulating lipoprotein retention and provide evidence for improving Ax absorption via dietary modulation. [ABSTRACT FROM AUTHOR]

ObjectiveMethodsResultsConclusionOmega-3 polyunsaturated fatty acids (PUFAs) play a crucial role in maintaining and improving cognitive function and brain health. The aim of this study was to assess the association between omega-3 PUFA intake and cognitive function in middle-aged and older adults in Saudi Arabia.Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). The frequency and quantity of omega-3 PUFA intake were assessed using an omega-3 food frequency questionnaire.A total of 175 participants were recruited for this study. Participants in the lowest omega-3 PUFA tertile group scored significantly lower in the visuospatial/executive and attention cognitive domains (p < 0.05). After adjusting for confounders, the higher intake of alpha-linolenic acid (ALA) was significantly associated with higher scores in the visuospatial/executive domain (p = 0.02) and the higher intake of docosahexaenoic acid (DHA) was significantly associated with higher scores in the attention domain (p = 0.04). The participants who did not consume walnuts showed a significant lower MoCA score than those who did (p = 0.005). No significant differences were found with other omega-3 PUFA sources.Higher intake of omega-3 PUFAs was positively associated with visuospatial/executive and attention cognitive functions in middle-aged and older adults. [ABSTRACT FROM AUTHOR]

Background: Following injury, older adults exhibit slow recovery of muscle function. Age-related impairment of sarcolemmal membrane repair may contribute to myocyte death, increasing the need for myogenesis and prolonging recovery. Dietary fish oil (FO) is a common nutritional supplement that may alter plasma membrane composition to enhance the response to membrane injury. Methods: We assessed effects of an 8-week dietary intervention on muscle contractile recovery in aged (22 mo.) rats on control (n = 5) or FO (control + 33 g/kg FO (45% eicosapentaenoic acid; 10% docosahexaenoic acid); n = 5) diets 1-week after contusion injury, as well as adult (8 mo., n = 8) rats on the control diet. Results: Recovery was reduced in aged rats on the control diet vs. adults (63 vs. 80%; p = 0.042), while those on the FO diet recovered similarly to (78%) adults. To directly assess sarcolemma injury, C2C12 cells were cultured in media with and without FO (1, 10, and 100 μg/mL; 24 or 48 h) and injured with an infrared laser in medium containing FM4-64 dye as a marker of sarcolemmal injury. FO reduced the area under the FM4-64 fluorescence-time curve at all concentrations after both 24 and 48 h supplementation. Conclusions: These preliminary data suggest FO might aid recovery of muscle function following injury in older adults by enhancing membrane resealing and repair. [ABSTRACT FROM AUTHOR]

Conjugated linoleic acid (CLA) isomers exhibit anti-inflammatory properties within the central nervous system (CNS). This study investigated the effects of CLA isomers c9,t11 and t10,c12 on fatty acid (FA) and N-acylethanolamine (NAE) profiles and their association with pro-inflammatory molecule expression in BV-2 microglia cell line, the CNS's resident immune cells responsible for maintaining neuronal activity and immune homeostasis. BV-2 cells were treated with 25µM of c9,t11-CLA, t10,c12-CLA, or oleic acid (OA) for 24 h, followed by lipopolysaccharide (LPS) stimulation. After treatment, the cell's FA and NAE profiles and pro-inflammatory molecule expression were analyzed. Our results demonstrated that CLA isomers mitigate LPS-induced morphological changes in BV-2 cells and reduce gene expression and protein levels of inflammatory markers. This effect was linked to an upregulation of acyl-CoA oxidase 1, a key enzyme in the anti-inflammatory peroxisomal beta-oxidation pathway that efficiently metabolizes CLA isomers. Notably, t10,c12-CLA significantly suppressed stearoyl-CoA desaturase 1, impacting monounsaturated fatty acid synthesis. The NAEs profile was remarkably altered by CLA isomers, with a significant release of the anti-neuroinflammatory mediator docosahexaenoic acid (DHA)-derived N-acylethanolamine (DHAEA). In conclusion, our findings suggest that the anti-neuroinflammatory effects of CLA isomers are due to their unique influences on FAmetabolismand themodulation of bioactive FA-derived NAEs, highlighting a potential strategy for nutritional intervention in conditions characterized by neuroinflammation. [ABSTRACT FROM AUTHOR]

Background: Schizochytrium, a group of eukaryotic marine protists, is an oleaginous strain, making it a highly promising candidate for the production of lipid-derived products such as biofuels and omega-3 fatty acids. However, the insufficient advancement of genetic engineering tools has hindered further advancements. Therefore, the development and application of genetic engineering tools for lipid enhancement are crucial for industrial production. Results: Transgene expression in Schizochytrium often encounters challenges such as instability due to positional effects. To overcome this, we developed a safe-harbor transgene expression system. Initially, the sfGFP gene was integrated randomly, and high-expressing transformants were identified using fluorescence-activated cell sorting. Notably, HRsite 2, located approximately 3.2 kb upstream of cytochrome c, demonstrated enhanced sfGFP expression and homologous recombination efficiency. We then introduced the 3-ketoacyl-ACP reductase (KR) gene at HRsite 2, resulting in improved lipid and docosahexaenoic acid (DHA) production. Transformants with KR at HRsite 2 exhibited stable growth, increased glucose utilization, and a higher lipid content compared to those with randomly integrated transgenes. Notably, these transformants showed a 25% increase in DHA content compared to the wild-type strain. Conclusion: This study successfully established a robust homologous recombination system in Schizochytrium sp. by identifying a reliable safe harbor site for gene integration. The targeted expression of the KR gene at this site not only enhanced DHA production but also maintained growth and glucose consumption rates, validating the efficacy of the safe-harbor approach. This advancement in synthetic biology and metabolic engineering paves the way for more efficient biotechnological applications in Schizochytrium sp. [ABSTRACT FROM AUTHOR]

AbstractThe incidence of Alzheimer’s is increasing and poses a significant social and economic burden. The pathogenesis involved in the expansion of AD includes neuronal oxidative damage, tau phosphorylation, amyloid beta aggregation, neuroinflammation, etc. Despite enormous efforts, there is currently no effective treatment or cure for this condition in the allopathic system. Marine compounds are appealing options and have a strong neuroprotective impact. Marine-derived compounds from sponges, algae, and marine invertebrates can be used for neuroprotection, with fewer adverse effects than synthetic drugs. Various compounds such as bryostatin-1, docosahexaenoic acid, spirolides, and astaxanthin, GV-971, have demonstrated outstanding activity and bioavailability. [ABSTRACT FROM AUTHOR]

This study elucidated the role of DHA-modulated genes in the development and growth of Atlantic bluefin tuna (Thunnus thynnus) larvae ingesting increasing levels of DHA in their rotifer prey. The effect of feeding low, medium, and high rotifer (Brachionus rotundiformis) DHA levels (2.0, 3.6 and 10.9 mg DHA g−1 DW, respectively) was tested on 2–15 days post hatching (dph) bluefin tuna larvae. Larval DHA content markedly (P < 0.05) increased in a DHA dose-dependent manner (1.5, 3.9, 6.1 mg DHA g−1 DW larva, respectively), that was positively correlated with larval prey consumption and growth (P < 0.05). Gene ontology enrichment analyses of differentially expressed genes (DEGs) demonstrated dietary DHA significantly (P < 0.05) affected different genes and biological processes at different developmental ages. The number of DHA up-regulated DEGs was highest in 10 dph larvae (491), compared to 5 (12) and 15 dph fish (34), and were mainly involved in neural and synaptic development in the brain and spinal cord. In contrast, DHA in older 15 dph larvae elicited fewer DEGs but played critical roles over a wider range of developing organs. The emerging picture underscores the importance of DHA-modulated gene expression as a driving force in bluefin tuna larval development and growth. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use of oil from Schizochytrium limacinum (strain FCC‐3204) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The extension of use pertains to the use of the NF as a food ingredient in protein products at a maximum use level of 1 g of docosahexaenoic acid (DHA) in 100 g of product. The Panel considers that the information provided on the composition and the production process is sufficiently described and does not raise safety concerns. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification 'for production purposes only'. Data provided demonstrated the absence of viable cells in the NF. Under the proposed extension of use, the highest intake estimate (at the 95th percentile) of DHA from the NF in protein products is 6.3 mg DHA/kg bw per day for adolescents. The Panel notes that the exposure to DHA from the new intended use of the NF in protein products is very low compared to the exposure to DHA from the already authorised food categories (excluding food supplements). The Panel concludes that the NF (oil from S. limacinum (FCC‐3204)) is safe under the new intended use. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia type 34 (SCA34) is a dominantly inherited disease that causes late-onset ataxia, in association with skin lesions in the form of erythrokeratodermia variabilis. It is caused by mutations in the ELOVL4 gene, which encodes for the ELOVL4 protein and has the function of lengthening very long chain (VLC) fatty acids (FA), which are important components of central myelin. The aim of this work was to review the medical literature on the biochemical abnormalities of SCA34, and based on the obtained information, to propose supplementation of deficient FAs. A review of the ad hoc medical literature was performed. Plasma levels of the ELOVL4 products C32, C34 and C36 FA have not been reported in SCA34 yet. However, pathogenic variants of ELOVL4 revealed deficient biosynthesis of C28, C30, C32, C34 and C36 FA compared to WT in cell cultures, and the levels of ceramides and phosphatidylcholines containing ≥ 34 C FA were decreased compared to WT in HeLa cells expressing mutant SCA34 proteins. Besides, a pathological study of SCA34 revealed myelin destruction and loss of oligodendrocytes in cerebral and cerebellar white matter. Levels of VLC-FA should be determined, to identify specifically deficient FAs in SCA34. Cerebellar ataxia could possibly be improved by administration of the deficient FAs, as found in SCA38 with supplementation of docosahexaenoic acid. The authors suggest investigators with access to SCA34, to take into consideration this therapeutic hypothesis, and try to verify the potential efficacy of administration of VLCFA in this disease. [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic gastrointestinal disorders associated with significant morbidity and complications. This study investigates the therapeutic potential of docosahexaenoic acid (DHA) in a trinitrobenzene sulfonic acid (TNBS) induced colitis model, focusing on inflammation, oxidative stress, and intestinal membrane permeability. Methods: Wistar albino rats were divided into Control, Colitis, and Colitis + DHA groups (n = 8–10/group). The Colitis and Colitis + DHA groups received TNBS intrarectally, while the Control group received saline. DHA (600 mg/kg/day) or saline was administered via gavage for six weeks. Macroscopic and microscopic evaluations of colon tissues were conducted. Parameters including occludin and ZO-1 expressions, myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), Interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels were measured in colon tissues. Results: Colitis induction led to significantly higher macroscopic and microscopic damage scores, elevated TOS levels, reduced occludin and ZO-1 intensity, decreased mucosal thickness, and TAS levels compared to the Control group (p < 0.001). DHA administration significantly ameliorated these parameters (p < 0.001). MPO, MDA, TNF-α, and IL-6 levels were elevated in the Colitis group but significantly reduced in the DHA-treated group (p < 0.001 for MPO, MDA; p < 0.05 for TNF-α and IL-6). Conclusion: DHA demonstrated antioxidant and anti-inflammatory effects by reducing reactive oxygen species production, enhancing TAS capacity, preserving GSH content, decreasing proinflammatory cytokine levels, preventing neutrophil infiltration, reducing shedding in colon epithelium, and improving gland structure and mucosal membrane integrity. DHA also upregulated the expressions of occludin and ZO-1, critical for barrier function. Thus, DHA administration may offer a therapeutic strategy or supplement to mitigate colitis-induced adverse effects. [ABSTRACT FROM AUTHOR]

Introduction: The relationship between blood N-3 polyunsaturated fatty acid (PUFA) levels and cardiovascular health is known, but direct evidence that N-3 PUFA levels influence electrocardiographic (ECG) parameters is non-existent. In the study described herein, we investigated the relationship between anthropometric biomarkers and capillary blood PUFAs with ECG outputs in a sample population of healthy pre-menopausal women. Method: Twenty-three consenting females were recruited, with the study power analysis sufficiently demonstrated. Food intake, anthropometric and cardiovascular parameters were obtained. Capillary blood was collected for fatty acid chromatographic analysis. Results: Body mass index, haematocrit, heart rate (HR), mean arterial pressure (MAP) and ECG readings all fell within healthy ranges. Principal component analysis-mediated correlations were carried out controlling for combined Components 1 (age, body fat % and waist-to-hip ratio) and 2 (height, HR and MAP) as control variables. Docosahexaenoic acid (DHA) unequivocally decreased the QRS area under the curve (AUC-QRS) regardless of the impact of control variables, with each unit increase in DHA corresponding to a 2.3-unit decrease in AUC-QRS. Mediation analysis revealed a significant overall effect of DHA on AUC-QRS, with the impact of DHA on R wave amplitude accounting for 77% of the total observed effect. Discussion: Our new findings revealed an inverse relationship between AUC-QRS with capillary blood DHA, suggesting that the association between ventricular mass and its QRS depolarising voltage is mediated by DHA. Our findings bridge a knowledge gap on the relationship between ventricular mass and ventricular efficiency. Further research will confirm whether the relationship identified in our study also exists in diseased patients. [ABSTRACT FROM AUTHOR]

Neural membranes are composed of phospholipids, sphingolipids, cholesterol, and proteins. In response to cell stimulation or injury, the metabolism of lipids generates various lipid mediators, which perform many cellular functions. Thus, phospholipids release arachidonic acid or docosahexaenoic acid from the sn-2 position of the glycerol moiety by the action of phospholipases A2. Arachidonic acid is a precursor for prostaglandins, leukotrienes, thromboxane, and lipoxins. Among these mediators, prostaglandins, leukotrienes, and thromboxane produce neuroinflammation. In contrast, lipoxins produce anti-inflammatory and pro-resolving effects. Prostaglandins, leukotrienes, and thromboxane are also involved in cell proliferation, differentiation, blood clotting, and blood vessel permeability. In contrast, DHA-derived lipid mediators are called specialized pro-resolving lipid metabolites (SPMs). They include resolvins, protectins, and maresins. These mediators regulate immune function by producing anti-inflammatory, pro-resolving, and cell protective effects. Sphingolipid-derived metabolites are ceramide, ceramide1-phosphate, sphingosine, and sphingosine 1 phosphate. They regulate many cellular processes, including enzyme activities, cell migration and adhesion, inflammation, and immunity. Cholesterol is metabolized into hydroxycholesterols and 7-ketocholesterol, which not only disrupts membrane fluidity, but also promotes inflammation, oxidative stress, and apoptosis. These processes lead to cellular damage. [ABSTRACT FROM AUTHOR]

BACKGROUND: Algae oil has garnered widespread acclaim due as a result of its high purity of docosahexaenoic acid (DHA) and excellent safety profile. The present study aimed to develop stable nanoemulsions (NEs) systems containing DHA from algae oil through thermal sterilization by combining modified whey protein concentrate (WPC) with low methoxyl pectin (LMP), as well as to investigate the impact of LMP concentration on the thermal stability and the gastrointestinal delivery efficiency of DHA NEs. RESULTS: The addition of LMP enhanced the stability of the emulsion after sterilization, at the same time as improving the protective and sustained release effects of DHA in the gastrointestinal tract. Optimal effect was achieved at a LMP concentration of 1% (10 g kg−1 sample), the stability of the emulsion after centrifugation increased by 17.21 ± 5.65% compared to the group without LMP, and the loss of DHA after sterilization decreased by only 0.92 ± 0.09%. Furthermore, the addition of 1% LMP resulted in a substantial reduction in the release of fatty acids from the NEs after gastrointestinal digestion simulation, achieving the desired sustained‐release effect. However, excessive addition of 2% (20 g kg−1 sample) LMP negatively impacted all aspects of the NEs system, primarily because of the occurrence of depletion effects. CONCLUSION: The construction of the LMP/WPC‐NEs system is conducive to the protection of DHA in algae oil and its sustained‐release in the gastrointestinal tract. The results of the present study can provide reference guidance for the application of algae oil NEs in the food field. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lack of n‐3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have demonstrated that different molecular forms of DHA are beneficial to brain development. The aim of this study was to investigate the effect of short‐term supplementation with DHA‐enriched phosphatidylserine (PS) and phosphatidylcholine (PC) on DHA levels in the liver and brain of congenital n‐3‐deficient mice. RESULTS: Dietary supplementation with DHA significantly changed the fatty acid composition of various phospholipid molecules in the cerebral cortex and liver while DHA‐enriched phospholipid was more effective than DHA triglyceride (TG) in increasing brain and liver DHA. Both DHA‐PS and DHA‐PC could effectively increase the DHA levels, but DHA in the PS form was superior to PC in the contribution of DHA content in the brain ether‐linked PC (ePC) and liver lyso‐phosphatidylcholine molecular species. DHA‐PC showed more significant effects on the increase of DHA in liver TG, PC, ePC, phosphatidylethanolamine (PE) and PE plasmalogen (pPE) molecular species and decreasing the arachidonic acid level in liver PC plasmalogen, ePC, PE and pPE molecular species compared with DHA‐PS. CONCLUSION: The effect of dietary interventions with different molecular forms of DHA for brain and liver lipid profiles is different, which may provide theoretical guidance for dietary supplementation of DHA for people. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare the efficacy of dietary intake of eicosapentaenoic acid (EPA; 20:5 ω-3) and docosahexaenoic acid (DHA; 22:6 ω-3) on very short sleep duration (<5 h/night) in adults. Methods: The bootstrap method was used in the multinomial logistic regression to estimate the ORs and corresponding 95% confidence intervals (CIs) of very short sleep duration. We used rolling window method to analyze the effects of EPA and DHA dietary intakes on very short sleep durations in men and women over age. To illustrate the stability of the results for the selected window width, we built a shiny application. Results: Compared to the first quartile, the mean ORs of EPA intake on very short sleep duration and the corresponding 95% CIs for the second, third and fourth quartiles of EPA intake among men under 32 years old were 1.50 (0.56, 3.44) mg, 1.55 (0.59, 3.48) mg, and 3.99 (1.15, 10.01) mg, respectively. Among women over 44 years old, the ORs for DHA intake were 1.12 (0.81, 1.52) mg, 0.94 (0.68, 1.29) mg, and 0.62 (0.38, 0.98) mg for the second, third and fourth quartiles, respectively. Conclusions: The associations of EPA and DHA with very short sleep duration are sex- and age-dependent. In males under the age of 32, a significant positive correlation exists between dietary EPA intake and very short sleep duration. For women above 44 years of age, an increase in DHA intake can notably ameliorate issues of very short sleep duration. [ABSTRACT FROM AUTHOR]

Sugarcane molasses is one of the by-products from the sugar industry, which is a candidate carbon source for microbes to produce high-value docosahexaenoic acid (DHA) that is beneficial to human health. The aim of this study was to optimize the sugarcane molasses medium for DHA production by Aurantiochytrium sp. and investigate the treatment and disposal of sugarcane molasses fermentation wastewater. Firstly, the sugarcane molasses volume ratio, carbon–nitrogen ratio and citric acid concentration were optimized for the sugarcane molasses medium, and the DHA production in Aurantiochytrium sp. R2A35 was increased from 2.63 to 7.48 g/L. Then, the two-staged oxygen supply strategy was adopted in the expanded culture, and the DHA production reached to 10.04 g/L. And the DHA proportion in total lipid was significantly improved from 41.08 to 60.46% (w/w), which promoted the total DHA production. The data showed that high oxygen supply promoted biomass accumulation and low oxygen supply promoted DHA accumulation in Aurantiochytrium sp. R2A35. It was also found that Aurantiochytrium sp. R2A35 preferred to use the reducing sugar in sugarcane molasses and then used sucrose. The final utilization rate of reducing sugar was 100% and the utilization rate of sucrose was 94.37%. Finally, the concentrated fermentation wastewater, sugarcane leaves and bagasse were mixed as a ratio of 2:5:12 for composting, and the compost product could meet the commercial organic fertilizer standard. This study accelerated the resource utilization of sugarcane waste and provided an alternative solution for DHA industry. [ABSTRACT FROM AUTHOR]

Background: Omega‐3 fatty acids (ω‐3 FA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are essential nutrients known for their anti‐inflammatory properties, which involve reducing pro‐inflammatory cytokines, eicosanoids, and insulin‐like growth factor‐1. This suggests their potential to alleviate acne severity, especially when deficits are present. Aims: To elevate EPA/DHA levels in acne patients through dietary intervention and supplementation, observing subsequent clinical effects. Methods: Over 16 weeks, 60 patients without prescription medication (n = 23 acne comedonica [AC], n = 37 acne papulopustulosa [AP]) adhered to a Mediterranean diet, incorporating oral algae‐derived ω‐3 FA supplementation (600 mg DHA/300 mg EPA week 1–8, 800 mg DHA/400 mg EPA week 8–16). At four visits (V1–V4), blood EPA/DHA levels were tracked using the HS‐omega 3 index® (EPA/DHA (%) of total identified fatty acids in erythrocytes; target 8%–11%, deficit <8%, severe deficit <4%), alongside clinical assessments and standardized questionnaires. Results: At baseline, 98.3% of patients had an EPA/DHA deficit, with the mean HS‐omega 3 index® rising from 4.9% at V1 to 8.3% at V4 (p < 0.001). AC showed significantly higher indices than AP at V4 (p = 0.035). Objective improvements in both inflammatory and non‐inflammatory lesions were observed (p < 0.001). While self‐reported appearance worsened in four patients, overall quality of life improved (p < 0.001), particularly in AP. Dietary triggers were more clearly defined than beneficial foods. Intake of cow's milk and dairy products reduced (p < 0.001). Compliance was good; no adverse events were reported. Conclusion: Many acne patients have a ω‐3 FA deficit. The HS‐omega 3 index® can be increased by a Mediterranean diet and oral supplementation with algae‐derived ω‐3 FA. Acne severity improved significantly in patients with target ω‐3 FA levels. [ABSTRACT FROM AUTHOR]

The composition of fatty acids in the muscle tissue of the unique Central Asian carp-like fish, Potanin Altai osman Oreoleuciscus potanini, was studied for the first time. The populations of these fish in the reservoirs of the semiarid zone (Durgun and Taishir) during the period of their formation are considered. It was shown that the content of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in O. potanini corresponds to the median of this value in the order Cypriniformes. It was established that the basis of the food web of the herbivorous form of this species consists of microalgae (diatoms, Euglena and, possibly, chrysophytes), as well as bacteria. At the same time, the levels of bacterial biomarkers, 15-17BCFA and 17:0 were significantly higher in fish in the Durgun reservoir, whereas the level of EPA (diatom biomarker) in O. potanini was higher in the Taishir reservoir. The established higher values of the heavy nitrogen isotope content in the muscles of O. potanini from the Taishir reservoir are most likely associated with the yet unformed benthic communities and with the incomplete diversification of the riverine form of the Potanin Altai osman into lacustrine forms. [ABSTRACT FROM AUTHOR]

For fish oil-free aquafeed development, a photoautotrophic microalga Tisochrysis lutea is believed to be the candidate source of n-3 highly unsaturated fatty acid (n-3 HUFA) because of its docosahexaenoic acid (DHA) biosynthesis. While DHA contents of T. lutea vary during the cultivation periods depending on algal growth phase, little is mentioned about how this dependence should be taken into consideration when evaluating the suitability of microalgae as an alternative to fish oil-formulated diets. Here, we compared nutritionally maximized cells of deceleration growth phase T. lutea and fish oils-formulated product (n-3 HUFA-enriched Chlorella) as a rotifer enrichment diet for enhancement in Japanese flounder Paralichthys olivaceus larviculture. T. lutea had higher concentrations of DHA in the polar lipids than those for enriched Chlorella. Such higher concentrations of T. lutea were estimated only in the deceleration growth phase (not in the logarithmic growth or stationary phase). When deceleration growth phase T. lutea were fed to Brachionus plicatilis rotifers previously cultured on unenriched Chlorella, the DHA of the rotifers was boosted up to the level in those fed with enriched Chlorella. Furthermore, use of T. lutea-fed rotifers for initial feeding of fish larvae enhanced the growth, survival, n-3 HUFA levels, and final juvenile productivity of the larvae as much as feeding the larvae with enriched Chlorella-fed rotifers. We propose that T. lutea in the deceleration growth phase are efficacious, fish oil-free sources of n-3 HUFA for marine fish larviculture. Highlights: Polar lipid DHA % was high in the deceleration growth phase of Tisochrysis lutea. DHA % was high in rotifers fed either T. lutea or fish oil-enriched Chlorella. Rotifers enriched with T. lutea improved marine fish larviculture performance. [ABSTRACT FROM AUTHOR]

Although supplementation with docosahexaenoic acid (DHA) during porcine oocyte IVM is well-established, the available data are limited due to the lack of consistency. Moreover, to our knowledge, the anti-oxidant effects of DHA on porcine oocytes have not been reported. Hence, this study aimed to examine the effects of DHA supplementation on the regulation of energy metabolism during porcine oocyte maturation to improve oocyte maturation and embryonic development. By supplementing the IVM medium with various DHA concentrations, 25 μM DHA was identified as the optimal concentration which improved intraoocyte glutathione content and enhanced embryonic development after parthenogenesis. Compared to embryos derived from the control group, those derived from SCNT or IVF showed significantly improved blastocyst formation upon DHA supplementation during IVM. In addition, various transcription factors associated with oocyte development and apoptosis in mature oocytes were beneficially regulated in the DHA-treated oocytes. Moreover, DHA improved the AMP-activated protein kinase (AMPK)-regulatory ability of porcine oocytes and ameliorated nuclear maturation and embryonic development, which were decreased by artificially downregulating AMPK. To our knowledge, this is the first study to examine the effects of DHA as an AMPK regulator on oocyte maturation and embryo development in pigs. Furthermore, DHA addition to the IVM medium upregulated the relative expression of genes associated with mitochondrial potential and lipid metabolism. Therefore, the membrane potential of mitochondria (evaluated based on the JC-1 aggregate/JC-1 monomer ratio) and the levels of fatty acids and lipid droplets in matured oocytes increased, resulting in increased ATP synthesis. In conclusion, the DHA treatment of porcine oocytes with 25 μM DHA during IVM enhances the homeostasis of energy metabolism by improving mitochondrial function and lipid metabolism, leading to improved quality of matured oocytes and enhanced embryonic developmental potential of in vitro produced (IVP) embryos. Thus, 25 μM DHA supplementation could serve as a tool for improving the quality of IVP embryos. The study findings provide a basis for further research on improving the production efficiency of cloned animals by securing high-quality matured oocytes and enhancing energy metabolism in mammalian oocytes, including those of pigs. • DHA (25 μM) optimally improves porcine oocyte quality and embryonic development. • DHA maintains the homeostasis of energy metabolism of porcine oocytes. • DHA improves pivotal functions of mitochondria in matured porcine oocytes. • DHA supplementation during porcine oocyte maturation improves lipid metabolism. [ABSTRACT FROM AUTHOR]

Intravenous lipid emulsions used in preterm infants contain insufficient docosahexaenoic acid (DHA) and arachidonic acid (ARA) to support normal development, resulting in deficiencies that contribute to complications of prematurity and cognitive delay. We sought to investigate the effects of new intravenous lipid emulsions designed to contain sufficient DHA and ARA to meet preterm needs, while avoiding liver toxicity. Three new lipid emulsions (NLE A-C) were laboratory-generated using high pressure homogenization. First, a long-term experiment evaluated the impact on plasma, liver, and frontal cortex fatty acid composition compared to commercially available lipid emulsions. Lipid emulsions were administered via daily orogastric gavage to four-week-old C57Bl/6 J mice. Next, liver toxicity was evaluated in a murine model of parenteral nutrition-induced hepatosteatosis. Mice were provided an ad lib fat-free high carbohydrate diet, with intravenous lipid emulsion administration every other day for 19 days. Administration of commercially available lipid emulsions (soybean oil, mixed oil, or fish oil) resulted in decreased plasma and tissue levels of DHA and/or ARA compared to a chow control. The new lipid emulsions demonstrated a dose-response effect in plasma and tissue concentration of DHA and ARA. NLE C (with an approximately even DHA:ARA ratio), compared to chow, maintained similar DHA (19.2 ± 0.3 vs. 19.3 ± 0.3%, P = 1.00) and ARA (10.4 ± 0.2 vs. 9.9 ± 0.2% ARA, P = 0.75) content in frontal cortex tissue. All three new lipid emulsions prevented biochemical liver injury and pathologist-assessed hepatosteatosis; soybean oil lipid emulsion and mixed oil lipid emulsion treatment resulted in hepatosteatosis in both experiments. Long-term treatment with the new lipid emulsions in juvenile mice resulted in increased plasma and tissue DHA and/or ARA content compared to currently available lipid emulsions. The new lipid emulsions also prevented hepatosteatosis and biochemical liver injury with enteral and parenteral administration. [ABSTRACT FROM AUTHOR]

A marine thraustochytrid, Aurantiochytrium, is a promising organism to produce docosahexaenoic acid (DHA) and squalene. Utilization of inexpensive substances such as proteins in wastes and by-products from the food industry for cultivation is a considerable option to reduce production cost; however, the proteolytic ability of Aurantiochytrium spp. is low compared to taxonomically close Shizochytrium aggregatum. We previously identified extracellular protease (extracellular protease 1, EP1) in S. aggregatum ATCC 28209 from the supernatant of the culture and found that a similar protease gene (EP2) was located downstream of the EP1 gene. In the present study, we created the transformants expressing SaEP1 and/or SaEP2 to enhance the proteolytic ability of Aurantiochytrium sp. 18W-13a strain and cultivated them in the medium containing casein as a test protein substrate. Through SDS-PAGE analysis, we confirmed that casein in the supernatant was more efficiently degraded by the transformants than the wild type, suggesting that the expressed protease(s) were properly expressed and excreted. After 4-day cultivation in the casein medium, the value of optical density at 660 nm and the cell number in the culture of the transformant that expressed both SaEP1 and SaEP2 (designated as EP12 strain) showed 1.48- and 1.38-fold higher than those of wild type, respectively. The DHA and squalene yield of the EP12 strain were respectively 158.3 and 0.23 mg L−1, and these values were 1.42- and 2.01-fold higher than those of wild type, respectively, suggesting that the EP12 created in the present study is a favorable strain for the cultivation using protein-containing medium. [ABSTRACT FROM AUTHOR]

Many marine benthic invertebrates have a pelagic life stage, during which larvae need to accumulate enough reserves to complete metamorphosis to a settled benthic juvenile. Currently, very little is known about how ocean conditions affect quality of the larvae. We studied this for three settlement seasons (2017–2019) by collecting returning Dungeness crab (Metacarcinus magister) megalopae at the Oregon coast and analyzing them for fatty acid biomarkers. We found that the larvae are omnivorous and have versatile diets. The daily larval abundance was positively correlated with larval quality. Despite the relatively high day‐to‐day variation, we found pronounced seasonal and inter‐annual differences in the body condition (size and total fatty acid content) and biomarker composition of megalopae. Especially, the early season recruits of 2017 had lower content of lipids and polyunsaturated fatty acids known to be beneficial to crustaceans. This is likely related to lingering effects of the eastern Pacific marine heat wave (2014–2016) on pelagic communities. The larvae were rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) with lower levels in benthic juveniles, indicating an ontogenetic diet shift and likely lower availability of DHA and EPA in the benthic environment. The pulsed megalopa recruitment may provide substantial carbon and lipid inputs to the nearshore ecosystem as a form of pelagic subsidy. Our results reveal that ocean conditions may have an effect on the quality of returning larvae, which likely influence their recruitment performance and early juvenile success, and thus potentially also the population size and commercial catch 4 yr later. [ABSTRACT FROM AUTHOR]

Background: The relationship between free fatty acids (FFAs) and the risk of mortality remains unclear. There is a scarcity of prospective studies examining the associations between specific FFAs, rather than total concentrations, of their effect on long-term health outcomes. Objective: To evaluate the correlation between different FFAs and all-cause and cardiovascular mortality in a large, diverse, nationally representative sample of adults in the US, and examine how different FFAs may mediate this association. Methods: This cohort study included unsaturated fatty acids (USFA) and saturated fatty acids (SFA) groups in the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 and provided blood samples for FFAs levels. Multiple model calibration was performed using Cox regression analysis for known risk factors to explore the associations between FFAs and all-cause and cardiovascular mortality. Results: In the group of USFA, 3719 people were included, median follow-up, 6.7 years (5.8–7.8 years). In the SFA group, we included 3900 people with a median follow-up, 6.9 years (5.9-8 years). In the USFA group, myristoleic acid (14:1 n-5) (hazard ratio (HR) 1.02 [1.006–1.034]; P = 0.004), palmitoleic acid (16:1 n-7) (HR 1.001 [1.001–1.002]; P < 0.001), cis-vaccenic acid (18:1 n-7) (HR 1.006 [1.003–1.009]; P < 0.001), nervonic acid (24:1 n-9) (HR 1.007 [1.002–1.012]; P = 0.003), eicosatrienoic acid (20:3 n-9) (HR 1.027 [1.009–1.046]; P = 0.003), docosatetraenoic acid (22:4 n-6) (HR 1.024 [1.012–1.036]; P < 0.001), and docosapentaenoic acid (22:5 n-6) (HR 1.019 [1.006–1.032]; P = 0.005) were positively associated with the all-cause mortality, while docosahexaenoic acid (22:6 n-3) had a statistically lower risk of all-cause mortality (HR 0.998 [0.996–0.999]; P = 0.007). Among the SFA group, palmitic acid (16:0) demonstrated a higher risk of all-cause mortality (HR 1.00 [1.00–1.00]; P = 0.022), while tricosanoic acid (23:0) (HR 0.975 [0.959–0.991]; P = 0.002) and lignoceric acid (24:0) (HR 0.992 [0.984–0.999]; P = 0.036) were linked to a lower risk of all-cause mortality. Besides 23:0 and 24:0, the other FFAs mentioned above were linearly associated with the risks of all-cause mortality. Conclusions: In this nationally representative cohort of US adults, some different FFAs exhibited significant associations with risk of all-cause mortality. Achieving optimal concentrations of specific FFAs may lower this risk of all-cause mortality, but this benefit was not observed in regards to cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Background: Docosahexaenoic acid (DHA) has been reported to be associated with the children's neurodevelopment, who may be exposed to tobacco smoke simultaneously. The evidence about joint effect of DHA intake and tobacco smoke exposure on children and adolescents' learning disabilities (LD) was limited. The objective of this study was to assess the joint effect of DHA intake and tobacco smoke exposure on children and adolescents' LD. Methods: A cross-sectional analysis of the NHANES 1999–2004 was performed. Children and adolescents aged 6–15 years old were included. The outcome was diagnosed by parental report of ever health professionals or school representative-identified LD. Dietary DHA intake data were obtained by food frequency questionnaire and tobacco smoke exposure levels were evaluated by serum cotinine levels. Weighted univariable and multivariate logistic regression analyses were conducted to determine the joint effect of DHA intake and tobacco smoke exposure on LD in children and adolescents, with odds ratios (ORs) and 95% confidence intervals (CIs). This joint association was further assessed after stratification by age, gender, body mass index, the history of attention deficit disorder and seen mental health professional. Results: We identified 5,247 children and adolescents in present study, of whom 593 (11.30%) had LD. After adjusting covariates, we observed children and adolescents with DHA intake (OR = 0.76, 95%CI: 0.61–0.96) was related to lower incidence of LD; children who exposure to tobacco smoke was related to higher incidence of LD (OR = 1.54, 95%CI: 1.07–2.23); children and adolescents who exposure to tobacco smoke and without DHA intake were related to highest odds of LD (OR = 2.08, 95%CI: 1.37–3.17, P for trend = 0.042), that was, DHA and tobacco smoke exposure may have a joint effect on the odds of LD in children and adolescents. Subgroup analyses suggested this joint effect was robust especially among children and adolescents with normal & underweight BMI and without the history of attention deficit disorder and seen mental health professional. Conclusion: Increasing the DHA intake and reducing tobacco smoke exposure may have a potential role in the prevention of LD in children and adolescents. This joint effect warrants further investigation by large-scale prospective study. [ABSTRACT FROM AUTHOR]

The total substitution of fishmeal (FM) and fish oil (FO) with sustainable feed ingredients, while maintaining acceptable growth performances and fish composition, is a challenge. Mussels have a high protein content, with essential amino acid and fatty acid (FA) profiles similar to those of FM. This study aimed to assess the potential to rear gilthead seabream (Sparus aurata) on a plant-based feed (without FM and FO) to which mussels were added. Subsequent effects on growth performance, protein content, and FA concentrations were studied. Juvenile gilthead seabream were reared for 46 days in water temperature of 21°C, in a recirculated aquaculture system composed of three fish tanks, each corresponding to one treatment: in the FMFO treatment, 342 fish were fed a commercial feed that contained FM and FO; in the plant-based feed (PBF) treatment, 345 fish were fed an experimental feed that contained only plant-based ingredients; in the mussel feed (MF) treatment, 342 fish were fed the feed from PBF supplemented with fresh mussel flesh from which the shells had been removed. Fish weighed a mean of 6.7 ± 1.3 g at stocking in each treatment. At harvest, the mean weight of fish from FMFO and MF were significantly different (23.1 ± 4.3 and 23.1 ± 5.2 g, respectively) than that from PBF (15.5 ± 3.6 g) (p < .05). Compared to the feed from FMFO, the feed from PBF decreased the percentages of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and saturated FA (14:0, 16:0) in fish, but increased those of 18:1, 18:2 n-6 and 18:3 n-3 FA. Compared to the feed from PBF, the feed from MF increased the EPA+DHA concentration in fish by 21%. Thus, adding fresh mussels to a plant-based feed yielded similar growth performances and survival rate as a commercial feed. It also improved the FA composition of fish compared to that of fish fed a plant-based feed. [ABSTRACT FROM AUTHOR]

The omega-3 polyunsaturated fatty acids (PUFAs) Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) exert multiple cardioprotective effects, influencing inflammation, platelet activation, endothelial function and lipid metabolism, besides their well-established triglyceride lowering properties. It is not uncommon for omega-3 PUFAs to be prescribed for hypertriglyceridemia, alongside antiplatelet therapy in cardiovascular disease (CVD) patients. In this regard, we studied the effect of EPA and DHA, in combination with antiplatelet drugs, in platelet aggregation and P-selectin and αIIbβ3 membrane expression. The antiplatelet drugs aspirin and triflusal, inhibitors of cyclooxygenase-1 (COX-1); ticagrelor, an inhibitor of the receptor P2Y12; vorapaxar, an inhibitor of the PAR-1 receptor, were combined with DHA or EPA and evaluated against in vitro platelet aggregation induced by agonists arachidonic acid (AA), adenosine diphosphate (ADP) and TRAP-6. We further investigated procaspase-activating compound 1 (PAC-1) binding and P-selectin membrane expression in platelets stimulated with ADP and TRAP-6. Both DHA and EPA displayed a dose-dependent inhibitory effect on platelet aggregation induced by AA, ADP and TRAP-6. In platelet aggregation induced by AA, DHA significantly improved acetylsalicylic acid (ASA) and triflusal's inhibitory activity, while EPA enhanced the inhibitory effect of ASA. In combination with EPA, ASA and ticagrelor expressed an increased inhibitory effect towards ADP-induced platelet activation. Both fatty acids could not improve the inhibitory effect of vorapaxar on AA- and ADP-induced platelet aggregation. In the presence of EPA, all antiplatelet drugs displayed a stronger inhibitory effect towards TRAP-6-induced platelet activation. Both omega-3 PUFAs inhibited the membrane expression of αIIbβ3, though they had no effect on P-selectin expression induced by ADP or TRAP-6. The antiplatelet drugs exhibited heterogeneity regarding their effect on P-selectin and αIIbβ3 membrane expression, while both omega-3 PUFAs inhibited the membrane expression of αIIbβ3, though had no effect on P-selectin expression induced by ADP or TRAP-6. The combinatory effect of DHA and EPA with the antiplatelet drugs did not result in enhanced inhibitory activity compared to the sum of the individual effects of each component. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION As unsaturated and saturated aldehydes, ketones are known to be responsible for off‐odors in surimi products, and they are mainly derived from lipid oxidation. Because surimi‐based products are rich in unsaturated fatty acids, they are prone to producing off‐odors during the refrigeration and reheating processes, which are common treatments for leftovers. The present study investigated the color, lipid oxidation productions, fatty acid profiles and volatile components in surimi gels during refrigeration at 4 °C for 3 days with multiple reheating.The results revealed that the accumulation rate of hydroperoxides was higher in the refrigeration stage, whereas the decomposition rate was higher during reheating in surimi gels. Both refrigeration and reheating treatments promoted conjugated diene values, acid values and carbonyl values. Nevertheless, reheating treatment decreased tohiobarbituric acid reactive substances and whiteness. The contents of unsaturated fatty acids, especially α‐linolenic acid, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, were reduced, whereas the contents of saturated fatty acids increased during refrigeration and multiple reheating. The unsaturated fatty acids were lost as a result of their oxidative deterioration. The volatile components profile showed that the accumulation of volatile components mainly occurred in the refrigeration stage. Multivariate data analysis was utilized to further clarify whether the off‐odors in surimi gels were mainly generated in refrigeration.Refrigeration and reheating both contributed to lipid oxidation and the generation of volatile compounds in surimi gels, but the off‐odors were mainly generated during refrigeration. This research provides a novel understanding of the formation of food odors in processing. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

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Several studies have explored the association between fish consumption during pregnancy and favorable neonatal outcomes, although some yield conflicting results. The American College of Obstetricians and Gynecologists recommends two to three servings of low-mercury fish per week for pregnant or breastfeeding women. However, fish can be a source of pollutants, like methylmercury, impacting neurological development. Conflicting studies on docosahexaenoic acid (DHA) supplementation exist in the literature, possibly due to varied supplement dosages. This survey, involving 501 women, investigated fish consumption and DHA supplement intake concerning gestational and neonatal outcomes. Notably, 92.1% of participants consumed fish weekly, with significant differences observed in gestational weight gain, birth weight, and length for those eating fish ≥3 times weekly compared to non-consumers. This study supports the recommendation for pregnant women to include fish in their diet while limiting exposure to environmental pollutants. Omega-3 fatty acid supplements are suggested to attain nutritional benefits without mercury risk. [ABSTRACT FROM AUTHOR]

Biofilms are considered a basal resource with high nutritional quality in stream food webs, as periphytic algae are abundant of polyunsaturated fatty acids (PUFAs). PUFAs are essential for growth and reproduction of consumers who cannot or have very limited capacity to biosynthesize. Yet, how the nutritional quality based on PUFA of basal food sources changes with light intensity remains unclear. We conducted a manipulative experiment in mesocosms to explore the response and mechanisms of nutritional quality to shading, simulating riparian restoration. We found a significant increase in PUFA% (including arachidonic acid, ARA) under shading conditions. The increased PUFA is caused by the algal community succession from Cyanobacteria and Chlorophyta to Bacillariophyta which is abundant of PUFA (especially eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA). On the other hand, shading increased PUFA via upregulating enzymes such as Δ12 desaturase (FAD2, EC:1.14.19.6) and 3-ketoacyl-CoA synthase (KCS, EC:2.3.1.199) in the biosynthesis of unsaturated fatty acid elongation pathways. Our findings imply that riparian reforestation by decreasing light intensity increases the nutritional quality of basal resources in streams, which may enhance transfer of good quality carbon to consumers in higher trophic levels through bottom-up effects. [ABSTRACT FROM AUTHOR]

Hybrid lemon fin barb is a crossed product between silver barb (Barbonymus gonionotus) and lemon fin barb (Hypsibarbus wetmorei). In the present study, the optimum dietary lipid requirement of larval hybrid lemon fin barb was examined using a total of 90 hybrid larvae (L) of 3-day-old (0.36 ± 0.01 mg). The larvae were stocked in triplicated 90 L tanks and fed with micro diets containing 0, 4, 8, 12, and 16% (FO 0, 4, 8, 12 and 16) dietary lipid levels for 20 days. While hybrid larvae fed non-lipid diet showed lowered survival and growth, larvae fed FO12 diet increased (p < .05) in weight gain, total length gain, specific growth rate, and protein efficiency ratio after 20 days. Hybrid larvae’s whole-body lipid content was increased with increasing dietary lipid level. Hybrid larvae consisted of significantly improved (p < .05) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and n-3 fatty acid contents at 12% dietary lipid. Excessive dietary lipids resulted in lipid droplets in enterocytes and swollen hepatocytes. The hybrid larvae fed non-lipid diet had shrunken hepatocytes. In conclusion, the optimum dietary lipid requirement for hybrid lemon fin barb larvae in terms of maximum growth is determined at 13.5% dietary fish oil by second-order polynomial analysis. [ABSTRACT FROM AUTHOR]

Antarctic krill (Euphausia superba) oil is attracting more interest for its nutritional as well as functional potentials. Nevertheless, its potential as new and innovative food component remains largely unexplored. This review aims to outline the chemical composition, extraction methods, and health advantages of krill oil, offering insights for its utilization and provides evidence why it is now on the spotlight. Krill oil presents a distinctive fat profile, rich in lipid classes, with phospholipids (PLs) comprising a significant portion (38.93—79.99%) with high levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Additionally, it includes several minor bioactive components like astaxanthin, tocopherols, sterols, flavonoids, and vitamin A. Various extraction technics, including solvent and solvent-free extraction, enzyme-assisted pretreatment extraction, super/subcritical fluid extraction, significantly influence both output as well as standard of the resulting product. Furthermore, the oil had been linked to a number of health advantages, including prevention of cardiovascular disease (CVD), anti-inflammatory effects, support for women's physiology, anticancer activities, as well as neuroprotection, among others. Despite the commercial availability of krill oil products as dietary supplement, there is a scarcity of studies exploring the underlying molecular mechanisms responsible for its various biological activities. Despite this, apply krill oil as an innovative food ingredient has not been thoroughly investigated. This review consolidates information on the chemical composition, extraction techniques, possible health advantages, as well as existing uses as applications, aiming to offer insights for its complete exploitation. In addition, it attempts to unravel the fundamental molecular mechanisms that being investigated to deeply understand how krill oil produces various biological effects. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionMedium-chain fatty acids (MCFAs) and docosahexaenoic acid (DHA) could affect the occurrence of mild cognitive impairment (MCI). β-hydroxybutyrate (BHB), mitochondrial DNA copy number (mtDNAcn) and mitochondrial DNA (mtDNA) deletions might be their potential mechanisms. This study aimed to explore the relationship between MCFAs, DHA and MCI, and potential mechanisms.This study used data from Tianjin Elderly Nutrition and Cognition (TENC) cohort study, 120 individuals were identified with new onset MCI during follow-up, 120 individuals without MCI were selected by 1:1 matching sex, age, and education levels as the control group from TENC. Conditional logistic regression analysis and mediation effect analysis were used to explore their relationship.Higher serum octanoic acid levels (OR: 0.633, 95% CI: 0.520, 0.769), higher serum DHA levels (OR: 0.962, 95% CI: 0.942, 0.981), and more mtDNAcn (OR: 0.436, 95% CI: 0.240, 0.794) were associated with lower MCI risk, while more mtDNA deletions was associated with higher MCI risk (OR: 8.833, 95% CI: 3.909, 19.960). Mediation analysis suggested that BHB and mtDNAcn, in series, have mediation roles in the association between octanoic acid and MCI risk, and mtDNA deletions have mediation roles in the association between DHA and MCI risk.Higher serum octanoic acid and DHA levels were associated with lower MCI risk. Octanoic acid could affect the incidence of MCI through BHB, then mitochondria function, or through mitochondria function, or directly. Serum DHA level could affect the incidence of MCI through mitochondria function, or directly. [ABSTRACT FROM AUTHOR]

Marine microalgae are the primary producers of ω3 polyunsaturated fatty acids (PUFAs), such as octadecapentaenoic acid (OPA, 18:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) for food chains. However, the biosynthetic mechanisms of these PUFAs in the algae remain elusive. To study how these fatty acids are synthesized in microalgae, a series of radiolabeled precursors were used to trace the biosynthetic process of PUFAs in Emiliania huxleyi. Feeding the alga with 14C-labeled acetic acid in a time course showed that OPA was solely found in glycoglycerolipids such as monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) synthesized plastidically by sequential desaturations while DHA was exclusively found in phospholipids synthesized extraplastidically. Feeding the alga with 14C-labeled α-linolenic acid (ALA), linoleic acid (LA), and oleic acid (OA) showed that DHA was synthesized extraplastidically from fed ALA and LA, but not from OA, implying that the aerobic pathway of DHA biosynthesis is incomplete with missing a Δ12 desaturation step. The in vitro enzymatic assays with 14C-labeled malonyl-CoA showed that DHA was synthesized from acetic acid by a PUFA synthase. These results provide the first and conclusive biochemistry evidence that OPA is synthesized by a plastidic aerobic pathway through sequential desaturations with the last step of Δ3 desaturation, while DHA is synthesized by an extraplastidic anaerobic pathway catalyzed by a PUFA synthase in the microalga. [ABSTRACT FROM AUTHOR]

Introduction: A diet rich in marine n-3 polyunsaturated fatty acids (PUFAs) may lower the risk of coronary heart disease and ischemic stroke. However, the association between intake of marine n-3 PUFAs and risk of hemorrhagic stroke has only been sparsely explored. We aimed to investigate the associations between intake of the major marine n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and their sum, in relation to incident hemorrhagic stroke and its subtypes, intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Methods: We analyzed data from the Danish Diet, Cancer and Health Cohort, which was established between 1993 and 1997. Information on dietary intake of marine n-3 PUFAs was obtained through a validated food frequency questionnaire. Potential hemorrhagic stroke cases were identified by linkage to the Danish National Patient Register and subsequently validated. Hazard ratios obtained by Cox proportional hazard regression analyses were used as measures of association. Results: A total of 394 subjects among 55,519 individuals developed hemorrhagic stroke during a median follow-up period of 13.5 years. In multivariable analyses including adjustment for established risk factors, we observed weak and statistically nonsignificant inverse associations between intake of EPA, DHA, and EPA + DHA and the rate of incident hemorrhagic stroke. In analyses of hemorrhagic stroke subtypes, we found indications of lower rates of ICH among participants in the highest quartile of EPA, DHA, and EPA + DHA compared with those in the lowest quartile and indications of lower rates of SAH in the highest quartile of EPA intake compared to the lowest quartile, but the findings were statistically nonsignificant. Conclusions: Inversely statistically nonsignificant associations were found between EPA, DHA, and EPA + DHA and hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP), a potentially blinding disease, is increasing worldwide because of the increased survival of extremely preterm and preterm infants born where oxygen monitoring and ROP screening programs are insufficient. Repeated retinal examinations are stressful for infants, and laser photocoagulation treatment for sight-threatening ROP is destructive. The use of anti-VEGF agents instead of lasers is widespread but requires a long-term follow-up because of late recurrence of the disease. In addition, the optimal anti-VEGF agent dosage and long-term systemic effects require further study. Summary: Interventions preventing ROP would be far preferable, and systemic interventions might promote better development of the brain and other organs. Interventions such as improved oxygen control, provision of fresh maternal milk, supplementation with arachidonic acid and docosahexaenoic acid, and fetal hemoglobin preservation by reducing blood sample volumes may help prevent ROP and reduce the need for treatment. Free readily available online tools to predict severe ROP may reduce unnecessary eye examinations and select, for screening, those at a high risk of needing treatment. Key Messages: Treatment warranting ROP is a sign of impaired neurovascular development in the central nervous system. Preventative measures to improve the outcomes are available. Screening can be refined using tools that can predict severe ROP. Laser treatment and anti-VEGF agents are valuable treatment modalities that may complement each other in recurrent ROP. [ABSTRACT FROM AUTHOR]

Docosahexaenoic acid (DHA, C22:6n-3) is an omega-3 fatty acid with beneficial effects for human health. In view of its increasing demand, DHA traditionally produced by marine fisheries will be insufficient, and an alternative sustainable source is urgently required. Here, we report the isolation and characterization of four novel microalgae strains, PLU-A, B, C and D, with a high DHA content of up to 45% from decayed mangrove samples collected from a coastal area in Singapore. Phylogenetic analysis revealed that these isolates were clustered with Schizochytrium sp. TK6 (OK244290.1) and were identified as Schizochytrium sp. strains. A medium optimization with Schizochytrium sp. PLU-D found a glucose-to-yeast extract ratio of 4:1 to be optimal for high biomass and lipid accumulation of up to 70% in shake flasks. In fed-batch fermentation scale-up with the Schizochytrium sp. PLU-D strain, this translates to 175 g/L dry biomass, 94 g/L lipid and 36.2 g/L DHA. Accordingly, the DHA titer obtained is superior to most of the scale-up production reported thus far, while the DHA content is comparable to two other commercially available DHA algae oils. These results suggest that Schizochytrium sp. PLU-D has high potential to be applied for the sustainable production of DHA. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with a higher prevalence of endometrial hyperplasia, thereby increasing the risk of endometrial and ovarian cancers. The precise mechanisms linking obesity to endometrial hyperplasia remain unclear, but dysregulation of adipose tissue homeostasis is known to play a significant role. Hypertrophied adipocytes in obese individuals secrete various bioactive substances, including cytokines, growth factors, hormones, and metabolites. Additionally, hyperplastic adipocytes exhibit enhanced aromatase activity, leading to increased estrogen synthesis, which further promotes the development of endometrial hyperplasia. Purpose: The purpose of this study is to explore the anti-inflammatory and anti-proliferative activities of the poly unsaturated fatty acids. Methodology: An extensive literature survey has been performed to identify the role of adipokines and elevated endogenous estrogen levels in activating cell survival signaling pathways, such as PI3K/Akt/mTOR, MEK/ERK1, and JAK–STAT in endometrial cells and their possible role in Endometrial Hyperplasia. Further, the possible beneficial anti-inflammatory and anti-proliferative effects of polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) were explored. Results: Numerous studies suggest the beneficial role of dietary fats, such as EPA, DHA, and AA in modulating the growth of endometrium in obesity-induced endometrial hyperplasia. PUFAs can activate adenosine monophosphate-activated protein kinase (AMPK), which inhibits gluconeogenesis and lipogenesis. It also phosphorylates acetyl-CoA, leading to a decrease in malonyl-CoA, which inhibits mitochondrial CPT1. Additionally, AMPK activation promotes β-oxidation, and PPAR-γ mechanisms by down regulating the NF-kB pathway involved in endometrial hyperplasia. Conclusion: This review sheds light on the potential of PUFAs in mitigating estrogen synthesis, adipokine secretion, and endogenous aromatase activity in obesity induced endometrial hyperplasia. Furthermore, it critically evaluates the role and mechanisms of PUFAs in attenuating obesity-associated endometrial hyperplasia and reducing the risk of ovarian cancer. [ABSTRACT FROM AUTHOR]

Introduction: It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI). Methods: This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA + DHA (FA 800 μg/d + DHA 800 mg/d), FA (800 μg/d), DHA (800 mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months. Results: During the 12-month follow-up, scores of full intelligence quotient (βDHA: 1.302, 95% CI: 0.615, 1.990, p < 0.001; βFA: 1.992, 95% CI: 1.304, 2.679, p < 0.001; βFA+DHA: 2.777, 95% CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA + DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA, and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05). Conclusions: Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone. [ABSTRACT FROM AUTHOR]