Recent advances on the physiological and pathophysiological roles of polyunsaturated fatty acids and their biosynthetic pathway.

Polyunsaturated fatty acids (PUFAs)-fatty acids containing multiple double bonds within their carbon chain-are an indispensable component of the cell membrane. PUFAs, including the omega-6 PUFA arachidonic acid (ARA; C20:4n-6) and the omega-3 PUFAs eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3), have been implicated in various (patho)physiological events. These PUFAs are either obtained from the diet or biosynthesized from the essential fatty acids linoleic acid (LA; C18:2n-6) and α-linolenic acid (ALA; C18:3n-3) via enzymatic reactions that are catalyzed by fatty acid elongases (ELOVL2 and ELOVL5) and fatty acid desaturases (FADS1 and FADS2). In this review, we summarize the recent literature studying the role of PUFAs, placing a special emphasis on the newly discovered functions of PUFAs and their biosynthetic pathway as revealed by studies using animal models targeting the PUFA biosynthetic pathway and genetic approaches including genome-wide association studies.

Differential Effect of Omega-3 Fatty Acids on Platelet Inhibition by Antiplatelet Drugs In Vitro.

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 αIIbß3 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 αIIbß3, 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 αIIbß3 membrane expression, while both omega-3 PUFAs inhibited the membrane expression of αIIbß3, 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.

Dysregulation of the Arachidonic Acid Pathway in Cystic Fibrosis: Implications for Chronic Inflammation and Disease Progression.

Cystic fibrosis (CF) is the most common fatal genetic disease among Caucasian people, with over 2000 mutations in the CFTR gene. Although highly effective modulators have been developed to rescue the mutant CFTR protein, unresolved inflammation and persistent infections still threaten the lives of patients. While the central role of arachidonic acid (AA) and its metabolites in the inflammatory response is widely recognized, less is known about their impact on immunomodulation and metabolic implications in CF. To this end, here we provided a comprehensive analysis of the AA metabolism in CF. In this context, CFTR dysfunction appeared to complexly disrupt normal lipid processing, worsening the chronic airway inflammation, and compromising the immune responses to bacterial infections. As such, potential strategies targeting AA and its inflammatory mediators are being investigated as a promising approach to balance the inflammatory response while mitigating disease progression. Thus, a deeper understanding of the AA pathway dysfunction in CF may open innovative avenues for designing more effective therapeutic interventions.

Extended-Spectrum Beta-Lactamase- and Plasmidic AmpC-Producing Enterobacterales among the Faecal Samples in the Bulgarian Community.

The aim of the present work was to genetically characterise cefotaxime-resistant enterobacteria isolated from community carriers in Bulgaria. In total, 717 faecal samples from children and adults in five medical centres in Sofia, Pleven and Burgas were examined. Antimicrobial susceptibility was evaluated by the disk diffusion method. blaESBL or plasmidic AmpC (pAmpC) genes were detected by PCR and sequencing. MLST and ERIC-PCR were used to detect clonal relatedness. Among the faecal samples, 140 cefotaxime-resistant enterobacteria were found. The most frequently detected species was Escherichia coli (77.9%, 109/140 samples), followed by Klebsiella pneumoniae (7.9%, 11/140). Among the isolates, blaCTX-M-15 (37.1%) was predominant, followed by blaCTX-M-3 (19.2%), blaCTX-M-14 (10%), and blaCTX-M-27 (4.3 %). Genes encoding pAmpC were observed in 11.4% (blaDHA-1, 16/140) and in 1.4% (blaCMY-2, 2/140). The frequency of ESBL and pAmpC producers among the subjects was 14.6% and 2.5%, respectively. No carbapenem-resistant isolates were found. Four main clonal complexes (CC131, CC10, CC38, and CC155) were detected among E. coli isolates. The most common type was ST131, phylogroup B2 (16.5%). The increased frequency of ESBL- and pAmpC-producing enterobacteria in the community is a prerequisite for treatment failures of the associated infections and a good background for further studies.

Dietary EPA and DHA enrichment of a high fat diet during doxorubicin-based chemotherapy attenuated neuroinflammatory gene expression in the brain of C57bl/6 ovariectomized mice.

Chemotherapy agents in breast cancer are associated with chemotherapy-related cognitive impairments (CRCI). Mechanisms are not fully clear, but alterations of glucose and lipid metabolism, neuroinflammation and neurodegeneration may contribute to CRCI. The aim of this study was to investigate the combined effects of a high fat (HF) diet combined with doxorubicin-based chemotherapy on glucose and lipid metabolism, neuroinflammation, and neurodegeneration in mice. Additionally, we examined the therapeutic potential of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to attenuate these effects. Female C57Bl/6 mice (n = 42) were fed HF, HFn-3 (2 % kcals as EPA + DHA) or Low Fat (LF) diets for seven weeks, with and without chemotherapy. In this study, two chemotherapy injections led to weight and body fat loss associated with a decrease in insulin resistance measured by HOMA-IR. HOMA-IR was significantly greater in HF versus LF groups; but HOMA-IR in HFn-3 group did not significantly differ from either HF or LF groups. Chemotherapy resulted in higher brain concentrations of the inflammatory chemokine KC/GRO. Compared to LF diet plus chemotherapy, HF diet plus chemotherapy upregulated multiple genes involved in neuroinflammation and neurodegeneration pathways. HFn-3 diet plus chemotherapy attenuated gene expression by downregulating multiple genes involved in neuroinflammation and blood brain barrier regulation, including Mapkapk2, Aqp4, and s100b, and upregulating Kcnb1 and Atxn3, genes involved in reduction of oxidative stress and anxiety, respectively. Overall, a HF diet combined with chemotherapy is associated with neuroinflammatory and neurodegenerative gene expression changes in this mouse model; dietary enrichment of EPA and DHA attenuated these effects. Further studies are needed to understand how diet impacts behavioral outcomes of CRCI.

[Digital health applications-What we should know as rheumatologists]. / Digitale Gesundheitsanwendungen ­ was sollten wir als Rheumatolog:innen wissen.

Digital health applications (DHAs) are revolutionising patient care by improving access to evidence-based therapy and promoting active self-management. The continuously growing number of DHAs enables patients to act more independently through digital support. The budget-neutral prescription and cost coverage by statutory health insurance companies reduce financial barriers for practitioners and patients. Initial studies show that DHAs can be used successfully to treat comorbidities and rheumatic diseases. Several DHAs for inflammatory rheumatic diseases are at an advanced stage of development. The identification of suitable patients and support through shared decision making are crucial for successful implementation. Challenges remain in adherence and acceptance of the applications. This article provides an overview of prescription in clinical routine, initial data and experiences from the reality of rheumatology care, and reports on current developments.

Efficacy of DHA-enriched phosphatidylserine and its underlying mechanism in alleviating polystyrene nanoplastics-induced hepatotoxicity in mice.

OBJECTIVE: Plastic pollution has become a global pollution problem that cannot be ignored. As the main destination of human oral intake, the toxic effects of plastic on the digestive system represented by the intestine and liver are the focus of current research. Marine-derived DHA-PS has a variety of biological activities, mainly focusing on improving brain function and regulating lipid metabolism. However, whether it has an improvement effect on PS-NPs-induced hepato-intestinal injury and the underlying mechanism remain unclear. METHODS: A murine liver injury model was established by gavage of PS-NPs for six weeks. By integrating approaches from lipidomics, transcriptomics, and gut microbiota analysis, the molecular mechanism by which DHA-PS alleviates PS-NPs-induced murine hepatotoxicity was explored through the "gut-liver axis". RESULTS: Our findings reveal that prolonged exposure to PS-NPs results in significant murine liver damage and dysfunction, characterized by increased oxidative stress and inflammation, along with exacerbated hepatic lipid accumulation. Mechanistically, PS-NPs disrupt the hepatic SIRT1-AMPK pathway by suppressing the expression of SIRT1, AMPKα, and PPARα, while enhancing the expression of SREBP-1c, ultimately leading to disordered hepatic lipid metabolism. The sphingolipid and glycerophospholipid metabolic pathways were particularly affected. Additionally, in agreement with transcriptomic analyses, PS-NPs activate the hepatic TLR4/NF-κB pathway. At the same time, exposure to PS-NPs decreases the expression of ZO-1, occludin, and claudin-1, diminishes the relative abundance of beneficial gut bacteria (norank_f_Muribaculaceae, Akkermansia, and norank_f_norank_o_Clostridia_UCG-014), and increases the prevalence of pathogenic gut bacteria (Coriobacteriaceae_UCG-002 and Desulfovibrio), exacerbating liver injury through the gut-liver axis. However, administering DHA-PS (50 mg/kg) effectively alleviated these injuries. CONCLUSION: This study was the first to employ multi-omics techniques to elucidate the potential mechanisms underlying hepatotoxicity induced by PS-NPs, thereby supporting the use of DHA-PS as a dietary supplement to mitigate the effects of nanoplastic pollutants.

Potential and metabolic impacts of double enrichments of docosahexaenoic acid and 25-hydroxy vitamin D3in tissues of broiler chickens.

BACKGROUND: Chicken may be enriched with 25-hydroxy D3 [25(OH)D3] and docosahexaenoic acid (DHA) to enhance dietary intakes of the public. OBJECTIVES: Two experiments were conducted to determine potential and metabolic impacts of enriching both DHA and 25(OH)D3 in tissues of broiler chickens. METHODS: In Expt. 1, 144 chicks (6 cages/treatment, 6 birds/cage) were fed a corn-soybean meal basal-diet (BD), BD+10,000 IU 25(OH)D3/kg [BD+25(OH)D3], BD+1% DHA-rich Aurantiochytrium (1.2 g DHA/kg; BD+DHA), or BD+25(OH)D3+DHA for 6 wk. In Expt. 2, 180 chicks were fed the BD, BD+DHA-rich microalgal oil (1.5 to 3.0 g DHA/kg, BD+DHA), BD+DHA + eicosapentaenoic acid (EPA)-rich microalgae (0.3 to 0.6 g EPA/kg, BD+DHA+EPA), BD+DHA+25(OH)D3 [6,000 to 12,000 IU/kg diet; BD+DHA+25(OH)D3], and BD+DHA+EPA+25(OH)D3 for 6 wk. RESULTS: Supranutrition of these two nutrients resulted in 57 to 62 mg of DHA and 1.9 to 3.3 µg of 25(OH)D3 per 100 g of breast or thigh muscles. The DHA enrichment was independent of dietary EPA or 25(OH)D3, but that of 25(OH)D3 in the liver was decreased (68%, P < 0.05) by dietary DHA in Expt. 1. Compared with BD, BD+25(OH)D3 enhanced (P < 0.05) gene expression related to D3 absorption (SRB1, NPC1L1) in the liver and D3 degradation (CYP24A1) in the breast and decreased mRNA or protein levels of vitamin D binding protein in the adipose tissue or thigh muscle. Supranutrition of DHA decreased mRNA levels of lipid metabolism-related genes (FADS1,2, ELOVL5, FADS2, FASN, and SREBP1). CONCLUSIONS: Both DHA and 25(OH)D3 were enriched in the muscles up to meeting 50% to 100% of the suggested intakes of these nutrients by consuming two servings of 100 g of fortified chicken. The enrichments altered gene expression related to lipid biosynthesis and vitamin D transport or storage.

Metagenomic Analysis to Assess the Impact of Plant Growth-Promoting Rhizobacteria on Peanut (Arachis hypogaea L.) Crop Production and Soil Enzymes and Microbial Diversity.

Peanut production could be increased through plant growth-promoting rhizobacteria (PGPR). In this regard, the present field research aimed at elucidating the impact of PGPR on peanut yield, soil enzyme activity, microbial diversity, and structure. Three PGPR strains (Bacillus velezensis, RI3; Bacillus velezensis, SC6; Pseudomonas psychrophila, P10) were evaluated, along with Bradyrhizobium japonicum (BJ), taken as a control. PGPR increased seed yield by 8%, improving the radiation use efficiency (4-14%). PGPR modified soil enzymes (fluorescein diacetate activity by 17% and dehydrogenase activity by 28%) and microbial abundance (12%). However, PGPR did not significantly alter microbial diversity; nonetheless, it modified the relative abundance of key phyla (Actinobacteria > Proteobacteria > Firmicutes) and genera (Bacillus > Arthrobacter > Pseudomonas). PGPRs modified the relative abundance of genes associated with N-fixation and nitrification while increasing genes related to N-assimilation and N-availability. PGPR improved agronomic traits without altering rhizosphere diversity.

Effect of supplementing algae to breeding and early gestation first calf heifers on growth and reproduction.

Fat supplementation has potential to improve reproductive performance and increase pregnancy rates in cattle by increasing the energy density of the diet. However, some of the positive effects of fat seem to be influenced by the type of fatty acid fed. Docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3) are long-chain n-3 poly-unsaturated fatty acids (PUFA) that have important biological effects on reproduction through their involvement in hormone and series 3 prostaglandin synthesis. Ruminant tissues are naturally almost devoid of n-3 long-chain PUFA, specifically EPA and DHA. Algae biomass provides a consistent source of DHA and EPA that could be fed to alter hormonal profiles and improve reproduction of beef heifers. Eighty-eight Angus × Simmental heifers (427 ± 1.8 kg BW) were blocked by BW and allotted to 2 treatments (44/treatment, 4 pens/treatment, 11 heifers/pen). Control heifers were fed a diet that contained (DM basis) 52.8% mixed grass silage, 32% corn silage, and 15.2% concentrate. DHAgold™ (49% fat; 21.8% DHA; DSM Inc.) was included in the algae diet at 1.65% of DM, replacing equal parts of corn and DDGS. Diets were formulated to contain 12% CP and 0.85 Mcal/kg NEg. Heifers were fed treatment diets from 54 d prior to the breeding season through the first trimester. Follicular fluid was collected on day 47 for hormonal analysis. Artificial insemination (AI) was from d 54 to 77. Heifers that did not get pregnant to AI were removed from the study on d 109 and placed with a bull. The study ended on d 180. Data were analyzed using the MIXED procedure of SAS. During the pre-breeding period, algae heifers had lesser DMI (P=0.006) compared to control heifers. Heifers supplemented with algae had greater ADG (P=0.03) during the breeding period and BW tended (P=0.06) to be greater for algae compared to control heifers on d 98 and was greater on d 180 (P=0.03). Dominant follicle diameter and follicular estrogen concentration were unaffected by treatment (P≥0.12). Follicular insulin-like growth factor-1 was greater in algae compared to control heifers (P=0.03). First service conception rate did not differ between treatments (P=0.67); however, second service and overall conception were lesser (P≤0.03) in algae compared to control heifers. These data suggest supplementing DHA-rich algae improved growth but decreased conception rates of primiparous beef females.

Association of EPA and DHA with age-related macular degeneration: a cross-sectional study from NHANES.

Purpose: This cross-sectional study conducted in the general US population investigated the association between dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the prevalence of AMD. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) were utilized, including 4,842 participants aged 40 years and older. Dietary EPA and DHA intake data were collected through two 24-h dietary recall interviews and adjusted for weight. AMD was determined by a standardized grading system based on the presence of key features of AMD in color photographs of the macula. Multivariate logistic regression and restricted cubic spline models evaluated the associations between dietary EPA and DHA intake and AMD. Subgroup analysis and interaction analysis explored the influence of covariates. Results: A total of 4,842 participants were included. In the multivariate-adjusted model 2, the odds ratios (ORs) with 95% confidence intervals (CIs) for AMD were 0.86 (0.75, 0.99) and 0.88 (0.80, 0.97) per unit increase in dietary EPA and DHA intake, respectively. Interaction testing revealed significant effect modification by age, education, and BMI on the EPA-AMD association, indicating these factors significantly impacted this inverse relationship (p-interaction < 0.05). Similarly, age, education, BMI, and cataract surgery history modified the inverse DHA-AMD association (p-interaction < 0.05). Dose-response analyses demonstrated a negative correlation between dietary EPA and DHA intake with AMD prevalence (p-nonlinearity = 0.184 and 0.548, respectively). Conclusion: Our findings suggested that higher dietary EPA and DHA intake could be associated with lower AMD risk in older US adults. Age, education level, BMI, and history of cataract surgery may influence this inverse association.

Complementary App-Based Yoga Home Exercise Therapy for Patients With Axial Spondyloarthritis: Usability Study.

BACKGROUND: Axial spondyloarthritis (AS) is a chronic inflammatory rheumatic disease characterized by potentially disabling inflammation of the spine and adjacent joints. Regular exercise is a cornerstone of treatment. However, patients with AS currently have little support. YogiTherapy (MaD Lab) is an app developed to support patients with AS by providing instructions for yoga-based home exercise therapy. OBJECTIVE: This study aimed to evaluate the usability and acceptance of the newly designed YogiTherapy app for patients with AS. METHODS: Patients completed the User Version of the Mobile Application Rating Scale (uMARS) and net promoter score (NPS) questionnaires after the app introduction. Wilcoxon Mann-Whitney rank sum test, chi-square test for count data, and correlation analysis were conducted to examine the usability of the app, acceptance, and patient characteristics. RESULTS: A total of 65 patients with AS (33, 51% female; age: mean 43.3, SD 13.6 years) were included in the study from May 2022 to June 2023. Subsequently, the data were analyzed. Usability was rated moderate, with a mean uMARS of 3.35 (SD 0.47) points on a scale from 0 to 5. The highest-rated uMARS dimension was information (mean 3.88, SD 0.63), followed by functionality (mean 3.84, SD 0.87). Females reported a significantly higher uMARS total score than males (mean 3.47, SD 0.48 vs mean 3.23, SD 0.45; P=.03, Vargha and Delaney A [VDA] 0.66, 95% CI 0.53-0.77). The mean average of the NPS was 6.23 (SD 2.64) points (on a scale from 0 to 10), based on 43% (26/65 nonpromoters, 42% (25/65) indifferent, and 15% (9/65) promoters. A total of 7% (5/65) of those surveyed did not answer the question. When applying the NPS formula, the result is -26%. The NPS showed a positive correlation with the usage of mobile apps (r=0.39; P=.02). uMARS functionality was significantly higher rated by patients younger than 41 years (mean 4.17, SD 0.55 vs mean 3.54, SD 1; P<.001; VDA 0.69, 95% CI 0.56-0.80). Patients considering mobile apps as useful reported higher uMARS (r=0.38, P=.02). The uMARS app quality mean score was correlated with the frequency of using apps (r=-0.21, P<.001). CONCLUSIONS: The results revealed moderate acceptance and usability ratings, prompting further app improvement. Significant differences were observed between age and gender. Our results emphasize the need for further improvements in YogiTherapy.

Lung Damage Induced by Plasmodium berghei ANKA in Murine Model of Malarial Infection is Mitigated by Dietary Supplementation with DHA-Rich Omega-3.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe complications that can occur in infections caused by any Plasmodium species. Due to the high lethality rate and the lack of specific treatment for ALI/ARDS, studies aimed at understanding and searching for treatment strategies for such complications have been fundamental. Here, we investigated the protective role of dietary supplementation with DHA-rich fish oil against lung damage induced by Plasmodium berghei ANKA in a murine model. Our results demonstrated that alveolar vascular damage, lung edema, and histopathological alterations were significantly reduced in mice that received dietary supplementation compared to those that did not receive the supplementation. Furthermore, a significant reduction in the number of CD8+ T lymphocytes, in addition to reduced infiltration of inflammatory cells in the bronchoalveolar lavage fluid was also observed. High levels of IL-10, but not of TNF-α and IFN-γ, were also observed in infected mice that received the supplementation, along with a reduction in local oxidative stress. Together, the data suggest that dietary supplementation with DHA-rich fish oil in malarial endemic areas may help reduce lung damage resulting from the infection, thus preventing worsening of the condition.

Effects of Dietary Lipid Levels on the Growth, Muscle Fatty Acid and Amino Acid Composition, Antioxidant Capacity, and Lipid Deposition in Mirror Carp (Cyprinus carpio).

In fish, increasing the crude lipid level of feed can save protein and improve feed utilization. Mirror carp (Cyprinus carpio) is one of the most widely farmed fish species in the world. In this study, mirror carp larvae were fed isonitrogenous diets with different lipid levels (3%, 5%, 7%, 9%, 11%, and 13%). The rearing trial lasted for eight weeks. The results revealed that when the fat content was 9%, the AWGR, WGR, and FCR were highest, whereas FCR was lowest. The AWGR was correlated with the dietary lipid level, and the regression equation was y = -2.312x2 + 45.01x + 214.49. Compared with those in the control group, the T-CHO and TG contents were significantly greater in the 13% lipid content groups and significantly lower in the 9% lipid content groups (p < 0.05). In terms of muscle quality, the contents of MUFAs, PUFAs, and DHA + EPA were significantly greater than those in the other experimental groups (p < 0.05). Oil red O staining revealed a lipid content of 13% with severe fat deposition. In addition, the results of the analysis of antioxidant enzyme activity revealed that the activities of GSH, CAT and T-AOC were significantly greater at the 9% lipid content, and that the MDA content was significantly greater at the 13% lipid content (p < 0.05). Similarly, the mRNA levels of GH, IGF-I, FAS, and LPL were significantly highest at a lipid level of 9% (p < 0.05). The above results revealed that the optimal dietary lipid requirement for the fast growth of mirror carp (6.86 ± 0.95 g) was 9.74% on the basis of nonlinear regression analysis of the AWGR. The dietary lipid level (9%) improved the growth, stress resistance, and lipid utilization of mirror carp to a certain extent.

SIRT1 and FOXO1 role on MASLD risk: effects of DHA-rich n-3 PUFA supplementation and exercise in aged obese female mice and in post-menopausal overweight/obese women.

Sirtuins 1 (SIRT1) and Forkhead box protein O1 (FOXO1) expression have been associated with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Exercise and/or docosahexaenoic acid (DHA) supplementation have shown beneficial effects on MASLD. The current study aims to assess the relationships between Sirt1, Foxo1 mRNA levels and several MASLD biomarkers, as well as the effects of DHA-rich n-3 PUFA supplementation and/or exercise in the steatotic liver of aged obese female mice, and in peripheral blood mononuclear cells (PBMCs) of postmenopausal women with overweight/obesity. In the liver of 18-month-old mice, Sirt1 levels positively correlated with the expression of genes related to fatty acid oxidation, and negatively correlated with lipogenic and proinflammatory genes. Exercise (long-term treadmill training), especially when combined with DHA, upregulated hepatic Sirt1 mRNA levels. Liver Foxo1 mRNA levels positively associated with hepatic triglycerides (TG) content and the expression of lipogenic and pro-inflammatory genes, while negatively correlated with the lipolytic gene Hsl. In PBMCs of postmenopausal women with overweight/obesity, FOXO1 mRNA expression negatively correlated with the hepatic steatosis index (HSI) and the Zhejiang University index (ZJU). After 16-weeks of DHA-rich PUFA supplementation and/or progressive resistance training (RT), most groups exhibited reduced MASLD biomarkers and risk indexes accompanying with body fat mass reduction, but no significant changes were found between the intervention groups. However, in PBMCs n-3 supplementation upregulated FOXO1 expression, and the RT groups exhibited higher SIRT1 expression. In summary, SIRT1 and FOXO1 could be involved in the beneficial mechanisms of exercise and n-3 PUFA supplementation related to MASLD manifestation.

ß-hydroxybutyrate and mitochondria mediate the association between medium-chain fatty acids, DHA and mild cognitive impairment: a nested case-control study.

BACKGROUND: Medium-chain fatty acids (MCFAs) and docosahexaenoic acid (DHA) could affect the occurrence of mild cognitive impairment (MCI). ß-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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Testing maternal effects of vitamin-D and omega-3 levels on offspring neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study.

BACKGROUND: Maternal vitamin-D and omega-3 fatty acid (DHA) deficiencies during pregnancy have previously been associated with offspring neurodevelopmental traits. However, observational study designs cannot distinguish causal effects from confounding. METHODS: First, we conducted Mendelian randomisation (MR) using genetic instruments for vitamin-D and DHA identified in independent genome-wide association studies (GWAS). Outcomes were (1) GWAS for traits related to autism and ADHD, generated in the Norwegian mother, father, and child cohort study (MoBa) from 3 to 8 years, (2) autism and ADHD diagnoses. Second, we used mother-father-child trio-MR in MoBa (1) to test causal effects through maternal nutrient levels, (2) to test effects of child nutrient levels, and (3) as a paternal negative control. RESULTS: Associations between higher maternal vitamin-D levels on lower ADHD related traits at age 5 did not remain after controlling for familial genetic predisposition using trio-MR. Furthermore, we did not find evidence for causal maternal effects of vitamin-D/DHA levels on other offspring traits or diagnoses. In the reverse direction, there was evidence for a causal effect of autism genetic predisposition on lower vitamin-D levels and of ADHD genetic predisposition on lower DHA levels. CONCLUSIONS: Triangulating across study designs, we did not find evidence for maternal effects. We add to a growing body of evidence that suggests that previous observational associations are likely biased by genetic confounding. Consequently, maternal supplementation is unlikely to influence these offspring neurodevelopmental traits. Notably, genetic predisposition to ADHD and autism was associated with lower DHA and vitamin-D levels respectively, suggesting previous associations might have been due to reverse causation.

Enrichment of EPA and DHA in glycerides by selective enzymatic ethanolysis.

It has been reported that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in glycerides have various biological functions. This study presents an effective method for enriching glycerides rich in EPA and DHA through lipase-catalyzed alcoholysis. The results showed that Eversa® Transform 2.0 had the strongest discrimination against DHA and EPA in alcoholysis, which was verified by molecular docking. Additionally, selectivity of the lipase and ratio of DHA and EPA in glyceride products were significantly affected by alcohol type. Under the optimal conditions, the contents of EPA and DHA in glycerides after ethanolysis reached 12.91 % and 55.40 %, respectively, with a DHA yield of 79.22 %. In this study, an interesting finding was that Eversa® Transform 2.0 could effectively differentiate EPA and DHA during alcoholysis to allow us to prepare DHA-enriched glycerides and EPA-enriched ethyl esters after removing saturated and monounsaturated ethyl esters.

Effect of Omega-3 Polyunsaturated Fatty Acid Supplementation on Clinical Outcome of Atopic Dermatitis in Children.

The use of omega-3 fatty acids (omega-3 FA) in the treatment of atopic dermatitis (AD) is an area of ongoing research. Some studies suggest that dietary supplementation with omega-3 FA can help manage symptoms of AD by reducing lesion severity, skin inflammation, dryness and itching, while others show no significant beneficial effect. The aim of this study was to evaluate the effect of omega-3 FA from fish oil in combination with gamma-linolenic acid (GLA) from blackcurrant seed oil in children with AD. This is a longitudinal, prospective, randomized, triple blind, placebo-controlled parallel clinical trial. The study was conducted during the 2-year period throughout autumn, winter, and spring, avoiding the summer when AD usually improves. Children were randomized to receive the active study product (Mega Kid®) containing a specific blend of omega-3 and omega-6 fatty acids or placebo. The primary outcomes were changes in severity of AD measured using SCORing Atopic Dermatitis (SCORAD), patient-oriented SCORAD (PO-SCORAD) and the difference in topical corticosteroid (TCS) use. The secondary outcomes were changes in itch intensity, sleep quality and Family Dermatology Life Quality Index (FDLQI). Data were analyzed for 52 children (26 in the intervention group and 26 in the placebo group). In children receiving the active product, intention-to-treat analysis showed that after 4 months of treatment, there was a significant decrease in the SCORAD index (from median 42 to 25, p < 0.001) and the use of topical corticosteroids (from median 30 to 10 mg/month, p < 0.001), but also significant improvements in itch, sleep quality, and overall quality of life. Omega-3 fatty acids in combination with GLA and vitamin D may decrease symptoms and were associated with an improvement clinical picture of AD in children. Therefore, we can conclude that supplementation with this specific combination could be considered a safe and effective intervention that may significantly reduce the severity of AD in pediatric patients.

Exploring the Therapeutic Potential of Omega-3 Fatty Acid Supplementation in Dry Eye Syndrome: An In vitro Investigation.

Background: Dry eye syndrome (DES) is a prevalent ocular condition characterized by insufficient tear production or excessive tear evaporation, leading to discomfort and visual disturbances. Omega-3 fatty acids have been proposed as a potential therapeutic intervention for DES due to their anti-inflammatory and lipid modulation properties. Materials and Methods: Cultured human corneal epithelial cells were exposed to various concentrations of omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for 72 h. Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while inflammatory cytokine levels (interleukin-6 (IL-6), interleukin-8 (IL-8)) and lipid profile (measured by lipid staining) were evaluated using enzyme-linked immunosorbent assay. Untreated cells served as controls for comparison. Results: Omega-3 fatty acid supplementation demonstrated a dose-dependent increase in cell viability compared to untreated cells. At optimal concentrations, EPA and DHA significantly enhanced cell viability by 30% and 35%, respectively (P < 0.05). Moreover, omega-3 fatty acid supplementation led to a significant reduction in inflammatory cytokine levels, with a 50% decrease in IL-6 and IL-8 secretion compared to untreated cells (P < 0.01). Additionally, lipid staining revealed improved lipid profile and organization in corneal epithelial cells following omega-3 fatty acid supplementation, indicative of enhanced tear film stability. Conclusion: In vitro findings suggest that omega-3 fatty acid supplementation exerts beneficial effects on cellular markers associated with DES.