Arachidonic Acid Ratio Research Articles

1234-P: Serum Fatty Acid Composition as a Biomarker of Diabetes Development: Tokushima Cohort Study

Few prospective cohort studies still exist on the association between serum fatty acid (FA) proportions and the enzymes involved in their synthesis and the onset of type 2 diabetes (T2D) . Thus, the aim of the present study was to investigate whether or not serum FA proportions or FA ratios, which reflect desaturase activities, are associated with the incidence of T2D. Here we analyzed data of a prospective cohort study, which was conducted during 2010-20in Japan. A total of 872 male workers without diabetes aged over 20 years were followed up prospectively. Diabetes was defined as having either: 1) fasting plasma glucose ≥ 126 mg/dl, 2) HbA1c ≥ 6.5%, 3) medication for hyperglycemia or 4) postprandial plasma glucose ≥ 200 mg/dl during the follow-up period. We measured serum FA levels and estimated the activity of ⊿5desaturase (D5D) by calculating the ratio of serum arachidonic acid to dihomo-γ-linolenic acid (DGLA) . The subjects were also divided into two groups by the cutoff point of waist circumference (WC) ≥ 90 cm. In multivariate analysis, the HR of developing diabetes was 2.81 [95%CI: 1.to 7.15, P=0.03] in the highest quartile of serum DGLA proportion and 0.28 [95%CI: 0.to 0.90, P=0.03] in the highest quartile of D5D, compared with their lowest quartiles, respectively. In stratified analysis, the multivariate adjusted risk of diabetes was higher in participants with low D5D/low WC (2.56 [0.96 to 6.82]) or high D5D/high WC (2.77 [0.68 to 11.32]) , and was significantly higher in participants with low D5D/high WC (6.30 [1.95 to 20.33, P=0.002]) than in participants with high D5D/low WC. Our findings suggest that the combination of increased serum DGLA proportion and attenuated D5D activity is a risk factor for the incidence of diabetes in male Japanese, especially in those with WC ≥ 90 cm. Thus, the significance of serum FA measurements in predicting T2D is suggested. Disclosure A.Hata: None. N.Aki: None. T.Ichihara: None. A.Tamura: None. T.Minagawa: None. Y.Kuwamura: None. M.Funaki: Board Member; Mechanogenic, Inc. Funding Grants-in-aid for research from Tokushima Prefecture Local Government

Severe Asymptomatic Essential Fatty Acid Deficiency (EFAD) in a Patient Enrolled in a Quality Improvement Project for HPN Patients (QIP-PN)

ObjectivesIntroduction. A 97-year-old, 47 kg female with a history of dysphasia, and failed enteral feeding was on HPN for 35 months. PN provided 150 grams dextrose, 75 grams amino acids, electrolytes, MVI and trace elements. Intravenous lipid emulsion (ILE) was held because liver dysfunction and line infections.MethodsThe patient enrolled in Amerita QIP-PN program. Essential fatty acid and trace element levels were obtained.ResultsSevere deficiencies of linoleic (c18:2w6; 524.3; (nl) 2653.4–6130.3 umol/L) and ἀ-linolenic acids (c18:3w3; 4.12; nl 26.1–150.1) were detected. Eicosatrienoic (Mead) acid (c20:3w9) was markedly elevated at 135.33 (nl 10.3–41.3). The eicosatrienoic to arachidonic acid (triene to tetraene) ratio was markedly elevated (0.27; nl 0.02–0.05). Stearic (267.2; nl 590.2 – 1377.2) and arachidic (8.86; nl 16.8 – 38.5) acids were low. Total polyunsaturated (1.6; nl 3.57 – 8.11) and total n-6 fatty acids (1.3; nl 3.3 – 7.1) were low. Seven fatty acid levels were elevated, apparently from de novo lipogenesis in the presence of insulin: myristic = 299.15 (nl 39.4 – 258.2), hexadecanoic = 300.41(nl 19.82 – 59.93), palmetoleic = 1197.60 (nl 68.5 – 570.2), vaccenic = 458.11 (nl 84.82 – 260.8), docosapentanoic = 32.8 (nl 9.2–32.1), docosenoic = 20.88 (nl 5.73 – 11.92). Interventions. Four-oil ILE was added as 20 grams once weekly, providing ∼4 grams of linoleic and ∼0.5 grams of ἀ-linolenic acids. Follow up free fatty acids showed normalization of ἀ-linolenic (27.07) and improvement in linoleic (889.74) and mead (60.34) acids. The triene to tetraene ratio improved to 0.17.ConclusionsAn elevated Mead acid level and elevated triene to tetraene ratio confirmed severe EFAD. Mead acid is produced from the elongation of oleic acid (n-9). The n-3, n-6, and n-9 fatty acids all compete for the same desaturases. But the desaturase enzymes have a preference for the fatty acids based on their n-terminal structure. The sequence is n-3 > n-6 > n-9. Therefore, increased Mead acid (20:3n-9) synthesis occurs only with very low availability of n-3 and n-6 fatty acids. In severe EFAD, Mead acid serves as a precursor to specific prostaglandins and leukotrienes via the cycloxygenase and lipoxygenase pathways. This case highlights the value of the QIP-PN in identifying EFAD in long-term HPN patients.Funding SourcesNone.

475-P: Plasma Fatty Acid Composition Is Associated with Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Patients

Type 2 diabetes is frequently complicated by nonalcoholic fatty liver disease (NAFLD) , which is mainly caused by high-fat and high-calorie diets, and obesity. In this regard, both the quantity and quality of fat accumulating in the liver are important, and in particular, the proportion of each fatty acid may be an important biomarker for NAFLD. We investigated whether serum fatty acid composition, especially n-6 polyunsaturated fatty acid (PUFA) and, saturated fatty acid (MUFA) and desaturase activity are associated with NAFLD in type 2 diabetes patients. Eighty-five type 2 diabetes patients (age: 60.3±13.9 years, BMI 27.5±5.8 kg/m2) who had no history of alcohol drinking, and had a negative result for hepatitis viruses were included as study subjects. Fatty liver (FL) was diagnosed based on liver ultrasonographic findings. Patients with FL were included in the FL group (n=51) , whereas those without FL included in the non-FL group (n=34) . Serum fatty acid levels were measured using gas chromatography. Desaturase activity for n-6 PUFAs was calculated as the ratio of arachidonic acid to dihomo-gamma-linolenic acid (DGLA) for Δ5 desaturase (D5D) . Waist circumference, BMI, serum triglyceride (TG) concentration, and ALT level were significantly higher in the FL group than in the non-FL group. The FL group also demonstrated higher levels of palmitic acid (PAL) and stearic acid (STA) , PAL/STA ratio, and DGLA than the non-FL group. In the FL group D5D activity was significantly lower than that in the non-FL group. PAL level, DGLA, and PAL/STA ratio showed a significant positive correlation with TG and ALT levels. Multiple regression analysis showed that DGLA was independently associated with FL development. These results suggest that type 2 diabetes patients with NAFLD have changes in their blood fatty acid profile, especially increased DGLA and PAL levels. The high levels of blood DGLA indicate downregulation of n-6 PUFA metabolism, probably caused by the decreased activity of D5D. Disclosure M.Higa: None. T.Ichijo: None.

Eicosanoid production by macrophages during inflammation depends on the M1/M2 phenotype

Macrophages are important in inflammation, and are involved in many physiological and pathological processes. Additionally, macrophages are important producers of eicosanoids, lipids that influence the inflammatory response. Our study aimed to explore the role of eicosanoids in the inflammatory response by studying the production of eicosanoids by macrophages on different stages of inflammation. Murine peritoneal macrophages (MPMs) were obtained at different stages of inflammation, which were then cultured in vitro with polyunsaturated fatty acids. Eicosanoids in MPMs were then detected by liquid chromatography–mass spectrometry. The metabolites derived from the cyclooxygenase (COX) pathway were increased, whereas those from the lipoxygenase (LOX) pathway were reduced. Additionally, the ratio of arachidonic acid (AA)-derived and eicosapentaenoic acid (EPA)-derived eicosanoids was dependent on the stage of inflammation. Moreover, the composition of macrophages with different phenotypes changed. To clarify the relationship between the phenotypes of macrophages and eicosanoids metabolism, we detected the eicosanoids in M1 and M2 differentiated THP-1 cells. Overall, M1 preferred AA, whereas M2 preferred EPA as substrate, which was related to the expression of COX and LOX. In conclusion, this study demonstrates that the difference in macrophage eicosanoids metabolism during the inflammatory response is related to the macrophage polarisation.

Role of omega 3 and omega 6 poly unsaturated fatty acids (PUFA) and vitamin D deficiency as risk determinants of metabolic syndrome in obesity: Worksite based case-control observational study

Background and aimsRisk factors for metabolic syndrome among obese population are not clear. The role of Eicosapentaenoic acid (EPA), Arachidonic acid (AA) Poly Unsaturated Fatty Acids (PUFA), their ratio and vitamin D deficiency as risk factors of metabolic syndrome (MS) was explored in obese worksite workers. MethodsThe 145 obese worksite workers were enrolled and MS was diagnosed using adult treatment panel III criteria. The levels of EPA, AA PUFA were estimated using liquid chromatography-Mass Spectrometer and vitamin D levels with ELISA method. The association of MS with the tertiles of EPA, AA PUFAs, their ratio and vitamin D was estimated by calculating odds ratio and 95% C.I., taking lowest tertiles as the reference group using logistic regression model adjusted for age and gender. Results105 out of 145 obese worksite workers; 72.4%, 95% C.I. (64.5%, 79.5%) had metabolic syndrome. The odd of MS was significantly lower in the group having highest tertiles of EPA 0.24 (0.09, 0.71) and was higher 2.0 (1.02, 3.89) in subjects with highest tertiles of AA: EPA ratio. The AA PUFA and vitamin D levels had no significant association with MS. ConclusionThe low levels of omega 3 PUFA (EPA) and elevated ratio of AA: EPA PUFA was significantly associated with MS in obese works site workers.

Association of fish oil containing lipid emulsions with retinopathy of prematurity: a retrospective observational study

BackgroundRetinopathy of prematurity (ROP) remains a leading cause of childhood blindness worldwide. This study aimed to investigate whether supplementation of n-3 polyunsaturated fatty acids (n-3 PUFAs) in parenteral nutrition may have beneficial effects on ROP in preterm infants.MethodsA total of 89 preterm infants, admitted to Neonatal Intensive Care Unit (NICU) in Anhui Provincial Children’s Hospital from September 2017 to August 2020, were recruited in the study. Based on the medical documents, the subjects were categorised into two groups: administration of the fish oil emulsion (n=43) containing soy oil, medium-chain-triglycerides (MCT), olive oil and fish oil (6g/dL, 6g/dL, 5g/dL and 3g/dL respectively), and the soy oil emulsion (n=46) containing 10g/dL of soy oil and MCT each. At 4 weeks of hospitalization, ROP was screened and diagnosed. Fatty acids in erythrocytes were determined using gas chromatography.ResultsThe averaged birth weight and gestational age were 1594±296 g and 31.9±2.3 wk, 1596±263 g and 31.6±2.3 wk respectively for preterm infants in the fish oil group and soy oil group. After 4 to 6 weeks of hospitalization, among all the preterm infants, 52 developed ROP (all stages) indicating an incidence of ROP at 58.43%. Although the incidence of ROP with any stages showed no differences between the two groups, the severe ROP incidence in the group with fish oil emulsions (2.33%) was significantly lower than that in the group with soy oil emulsions (23.91%) (P<0.05). After 14 days of nutrition support, the preterm infants administered fish oil emulsions had an increase in erythrocyte DHA content, with a reduction in ratio of arachidonic acid (AA) to DHA and an increase of n-3 index.ConclusionSupplementation of n-3 PUFAs through parenteral fish oil containing lipid emulsions resulted in an increase in erythrocyte DHA, and this might have beneficial effects on prevention of severe ROP in preterm infants.

Investigation on Cell Disruption Techniques and Supercritical Carbon Dioxide Extraction of Mortierella alpina Lipid.

Mortierella alpina, an oleaginous fungus, has been shown to be a potential source for arachidonic acid (ARA) production. The recovery of intracellular lipids from M. alpina is an important step for the downstream bioprocessing, and green extraction techniques with a focus on being efficient and eco-friendly have drawn much attention. In this study, different cell disruption techniques (mechanical: high-speed homogenization 10,000 rpm, ultrasonication 20 kHz, high-pressure process (HPP) 200–600 MPa; non- mechanical: acid treatment HCl) were investigated for lipid recovery from M. alpina, and process parameters (A. temperature, B. pressure, C. cosolvent ratio) of supercritical carbon dioxide (SC-CO2) lipid extraction were studied by applying response surface methodology (RSM). Compared with Soxhlet extraction as a control group (100%), high-speed homogenization has the highest lipid recovery (115.40%) among mechanical disruption techniques. Besides, there was no significant difference between high-speed homogenization and 1 M HCl treatment (115.55%) in lipid recovery. However, lipid recovery decreased to 107.36% as the concentration of acid was increased to 3 M, and acid treatment showed a negative effect on the ARA ratio. In HPP treatment, the highest lipid recovery (104.81%) was obtained at 400 MPa, 1 time of treatment and water medium. In the response surface model of SC-CO2 extraction, results showed the major influence of the process parameters to lipid recovery was pressure, and there are interaction effects of AC (temperature and cosolvent ratio) and BC (pressure and cosolvent ratio). Lipid recovery of SC-CO2 extraction reached 92.86% at 201 bar, 58.9 °C and cosolvent ratio 1:15. The microbial lipid recovery process of this study could be used as a reference and an eco-friendly alternative for the future downstream bioprocessing of ARA production by M. alpina.

Effect of Sea Salt and Taro Waste on Fungal Mortierella alpina Cultivation for Arachidonic Acid-Rich Lipid Production

Arachidonic acid (ARA), an important polyunsaturated fatty acid (PUFA), acts as a precursor for eicosanoid hormones, such as prostaglandins, leukotrienes and other biological substances in human and animal bodies. Mortierella alpina is considered to be a potential strain for ARA production. Using agricultural waste as a substrate for microbial fermentation could achieve biorefinery concepts, and sea water utilization of the cultivation process could help to conserve fresh water resources. The objectives of this study were to find a potential M. alpina strain for ARA production, to investigate the tolerance of salinity and to evaluate the feasibility of the taro waste hydrolysate for M. alpina cultivation. The result showed that M. alpina FU30797 had the highest lipid content (25.97%) and ARA ratio (34.60%) among three strains. Furthermore, there was no significant difference between 0 and 10 g/L of sea salt solution on the biomass concentration and lipid content of M. alpina FU30797. The acidic hydrolysate and enzymatic hydrolysate of taro peel waste (TPW) were both utilized as culture substrates by M. alpina FU30797; however, the substrate up-take rate and lipid content in the TPW enzymatic hydrolysate cultivation were 292.33 mg/L-h and 30.68%, respectively, which are higher than those in acidic hydrolysate cultivation, and the ARA ratio was 33.05% in the enzymatic hydrolysate cultivation. From fed-batch cultivation in the bioreactor, the lipid content and ARA ratio reached 36.97% and 46.04%, respectively. In summary, the results from this project could potentially provide useful information for developing the PUFA-ARA bioprocess by using M. alpina.

Sex-specific differences in plasma lipid profiles are associated with Gulf War Illness

BackgroundNearly 250,000 veterans from the 1990–1991 Gulf War have Gulf War Illness (GWI), a condition with heterogeneous pathobiology that remains difficult to diagnose. As such, availability of blood biomarkers that reflect the underlying biology of GWI would help clinicians provide appropriate care to ill veterans. In this study, we measured blood lipids to examine the influence of sex on the association between blood lipids and GWI diagnosis.MethodsPlasma lipid extracts from GWI (n = 100) and control (n = 45) participants were subjected to reversed-phase nano-flow liquid chromatography-mass spectrometry analysis.ResultsAn influence of sex and GWI case status on plasma neutral lipid and phospholipid species was observed. Among male participants, triglycerides, diglycerides, and phosphatidylcholines were increased while cholesterol esters were decreased in GWI cases compared to controls. In female participants, ceramides were increased in GWI cases compared to controls. Among male participants, unsaturated triglycerides, phosphatidylcholine and diglycerides were increased while unsaturated cholesterol esters were lower in GWI cases compared to controls. The ratio of arachidonic acid- to docosahexaenoic acid-containing triglyceride species was increased in female and male GWI cases as compared to their sex-matched controls.ConclusionDifferential modulation of neutral lipids and ratios of arachidonic acid to docosahexaenoic acid in male veterans with GWI suggest metabolic dysfunction and inflammation. Increases in ceramides among female veterans with GWI also suggest activation of inflammatory pathways. Future research should characterize how these lipids and their associated pathways relate to GWI pathology to identify biomarkers of the disorder.

Eicosapentaenoic acid/arachidonic acid ratio in Japanese junior high school students.

This epidemiological study investigated the eicosapentaenoic acid/arachidonic acid ratio (EAR) and docosahexaenoic acid/ arachidonic acid ratio (DAR) in ninth-graders in Japan. A total of 175 ninth-grade children from Tsunan Town (115 boys and 60 girls) were enrolled in the study between 2015 and 2017. All participants were assessed during annual health checkups to determine their EAR and DAR. All data were compared between boys and girls using the Mann-Whitney test. Spearman's rank correlation coefficient was used to describe the strengths of correlations between the EAR, DAR, and relevant parameters. The median (minimum, maximum) EAR and DAR of all participants were 0.13 (0.05, 0.46) and 0.47 (0.25, 0.84), respectively. There was no significant difference in the EAR between boys and girls at 0.12 (0.05, 0.46) and 0.13 (0.06, 0.27) (P = 0.375), respectively. The DAR was not significantly different (P = 0.125). There was a significant positive correlation between EAR and triglyceride, body mass index, and homeostasis model assessment but a significantly negative correlation with HbA1c (r = -0.209, P = 0.006). In contrast, there was no significant correlation between DAR and any parameters. This is the first epidemiological study investigating the EAR using a population-based cohort of Japanese adolescents. The EAR in boys/girls in Japan is 0.12 (0.05, 0.46)/0.13 (0.06, 0.27). The study results suggest that children with a healthy diet may generally have a lower average blood glucose level.

Evaluation of erythrocyte membrane fatty-acid compositions in association with interleukin-6 levels in patients with COVID-19

ObjectiveThe cytokine storm presented in the hyperimmune response is related to poor prognosis in people with COVID-19. Interleukin-6 (IL-6) is one of the most prominent cytokines, especially on mucosal surfaces during infection, causing the cytokine storm. Polyunsaturated fatty acids (PUFAs) are the precursors of eicosanoids, which play critical roles in immune regulation and inflammation. The balance between ω-3 and ω-6 levels in the cell membrane has a critical role in regulating the equilibrium between proinflammatory and antiinflammatory processes and inducing IL-6 production. The present study focused on inflammatory and antiinflammatory mechanisms in COVID-19 over PUFAs and on relating their levels with disease prognosis and severity. MethodsA total of 106 participants were included in the study. They were divided into three groups according to IL-6 level— 1: <35 pg/mL, 2: between 35 and 300 pg/mL, and 3: >300 pg/mL. Erythrocyte membrane PUFA compositions were analyzed by group. ResultsLevels of γ-linolenic acid and ω-6/ω-3 ratios were significantly increased in all comparison groups (P < 0.05). Total ω-6 and the ratio of arachidonic acid to eicosopentaenoic acid showed a statistically significant difference only between groups 1 and 3 (P < 0.05). There was a moderately negative correlation between total ω-3 and IL-6 and procalcitonin. There were positive correlations with ω-6/ω-3 ratio inflammatory markers, and the total ω-6 index also showed a moderately positive correlation with IL-6, procalcitonin, and D-dimer levels. ConclusionsThe ratio of arachidonic acid to eicosopentaenoic acid, and ω-3 PUFAs, can be systemic signs of poor prognosis, increased lung damage, and high mortality in COVID-19, together with IL-6.

Abstract 10822: Lower EPA/AA Ratio is Associated with a Higher Prevalence of Vulnerable Characteristics in Non-Culprit Coronary Plaques in Statin-Treated Patients with Coronary Artery Disease

Introduction: Low eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is associated with an increased risk of cardiovascular events in patients with coronary artery disease (CAD). However, the association between EPA/AA ratio and the characteristics of non-culprit coronary plaque in statin-treated patients with CAD remains to be elucidated. Hypothesis: Lower EPA/AA ratio is associated with a higher prevalence of vulnerable characteristics in non-culprit coronary plaque in statin-treated patients with CAD. Methods: A total of 367 consecutive stain-treated patients with stable coronary disease, who underwent percutaneous coronary intervention for the culprit lesion and optical coherence tomography (OCT) imaging of a non-culprit plaque in a culprit vessel were included. The characteristics of non-culprit plaque assessed by OCT were compared between the lower EPA/AA group (EPA/AA &lt;0.4, n=255) and the higher EPA/AA group (EPA/AA ≥0.4, n=112). Results: The prevalence of lipid-rich plaque (58.8 vs. 42.0%, p=0.004) and plaque with macrophage (56.1 vs. 32.1%, p&lt;0.001) was significantly higher in the lower EPA/AA group than in the higher EPA/AA group (Panel A). The lower EPA/AA was independently associated with the presence of lipid-rich plaque (Odds ratio [OR], 1.837; 95% confidence interval [CI]: 1.130-3.004, p=0.015) and plaque with macrophage (OR, 2.764; 95% CI: 1.672-4.639, p&lt;0.001) (Panel B). Conclusions: Lower EPA/AA ratio was associated with a higher prevalence of vulnerable characteristics in non-culprit plaque. The present results may partly explain the impact of low EPA/AA ratio on the increased incidence of recurrent events in patients with CAD.

Greater Change in the Eicosapentaenoic Acid to Arachidonic Acid Ratio Is Associated With Decreased Incidence of Cardiovascular Events in Acute Coronary Syndrome Patients With Elevated Triglyceride Levels.

This study investigated whether the percentage change (%Δ) in the eicosapentaenoic acid to arachidonic acid (EPA/AA) ratio is associated with cardiovascular event rates among acute coronary syndrome (ACS) patients receiving contemporary lipid-lowering therapy other than polyunsaturated fatty acids (PUFAs).Methods and Results:This post hoc subanalysis of the HIJ-PROPER study included PUFA-naïve patients for whom EPA/AA ratio data were available at baseline and after 3 months. Patients were categorized into 2 groups based on the median %ΔEPA/AA ratio: Group 1, change less than the median; and Group 2, change greater than or equal to the median. The 3-year rates of the primary endpoint, a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and unstable angina pectoris, were compared between the 2 groups. The median %ΔEPA/AA ratio in Groups 1 and 2 was -26.2% (n=482 patients [49.9%]) and 42.2% (n=483 patients [50.1%]), respectively. At the 3-year follow-up, the occurrence of the primary endpoint was significantly lower in Group 2 than in Group 1 (29/483 [6.0%] vs. 53/482 [11.0%]; hazard ratio 0.53, 95% confidence interval 0.33-0.82; P=0.005). The same trend was observed after adjusting for patient factors (P=0.02). Among ACS patients receiving contemporary lipid-lowering therapy other than PUFAs, a greater change in the EPA/AA ratio was associated with a lower incidence of cardiovascular events.

FABP7 Facilitates Uptake of Docosahexaenoic Acid in Glioblastoma Neural Stem-like Cells.

Glioblastoma (GBM) is an aggressive tumor with a dismal prognosis. Neural stem-like cells contribute to GBM’s poor prognosis by driving drug resistance and maintaining cellular heterogeneity. GBM neural stem-like cells express high levels of brain fatty acid-binding protein (FABP7), which binds to polyunsaturated fatty acids (PUFAs) ω-6 arachidonic acid (AA) and ω-3 docosahexaenoic acid (DHA). Similar to brain, GBM tissue is enriched in AA and DHA. However, DHA levels are considerably lower in GBM tissue compared to adult brain. Therefore, it is possible that increasing DHA content in GBM, particularly in neural stem-like cells, might have therapeutic value. Here, we examine the fatty acid composition of patient-derived GBM neural stem-like cells grown as neurosphere cultures. We also investigate the effect of AA and DHA treatment on the fatty acid profiles of GBM neural stem-like cells with or without FABP7 knockdown. We show that DHA treatment increases DHA levels and the DHA:AA ratio in GBM neural stem-like cells, with FABP7 facilitating the DHA uptake. We also found that an increased uptake of DHA inhibits the migration of GBM neural stem-like cells. Our results suggest that increasing DHA content in the GBM microenvironment may reduce the migration/infiltration of FABP7-expressing neural stem-like cancer cells.

Consumption of Monounsaturated Fatty Acids Is Associated with Improved Cardiometabolic Outcomes in Four African-Origin Populations Spanning the Epidemiologic Transition.

Long-chain omega-3 PUFAs, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are of increasing interest because of their favorable effect on cardiometabolic risk. This study explores the association between omega 6 and 3 fatty acids intake and cardiometabolic risk in four African-origin populations spanning the epidemiological transition. Data are obtained from a cohort of 2500 adults aged 25–45 enrolled in the Modeling the Epidemiologic Transition Study (METS), from the US, Ghana, Jamaica, and the Seychelles. Dietary intake was measured using two 24 h recalls from the Nutrient Data System for Research (NDSR). The prevalence of cardiometabolic risk was analyzed by comparing the lowest and highest quartile of omega-3 (EPA+ DHA) consumption and by comparing participants who consumed a ratio of arachidonic acid (AA)/EPA + DHA and >4:1. Data were analyzed using multiple variable logistic regression adjusted for age, gender, activity, calorie intake, alcohol intake, and smoking status. The lowest quartile of EPA + DHA intake is associated with cardiometabolic risk 2.16 (1.45, 3.2), inflammation 1.59 (1.17, 2.16), and obesity 2.06 (1.50, 2.82). Additionally, consuming an AA/EPA + DHA ratio of >4:1 is also associated with cardiometabolic risk 1.80 (1.24, 2.60), inflammation 1.47 (1.06, 2.03), and obesity 1.72 (1.25, 2.39). Our findings corroborate previous research supporting a beneficial role for monounsaturated fatty acids in reducing cardiometabolic risk.

Association between Preoperative Long-Chain Polyunsaturated Fatty Acids and Oxidative Stress Immediately after Total Knee Arthroplasty: A Pilot Study.

Quadriceps muscle atrophy following total knee arthroplasty (TKA) can be caused by tourniquet-induced ischemia–reperfusion (IR) injury, which is often accompanied by oxidative stress and inflammatory responses. n-3 long-chain polyunsaturated fatty acids (LCPUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert antioxidant and anti-inflammatory effects against IR injury, whereas n-6 LCPUFAs, particularly arachidonic acid (AA), exhibit pro-inflammatory effects and promote IR injury. This study aimed to examine whether preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio are associated with oxidative stress immediately after TKA. Fourteen eligible patients with knee osteoarthritis scheduled for unilateral TKA participated in this study. The levels of serum EPA, DHA, and AA were measured immediately before surgery. Derivatives of reactive oxygen metabolites (d-ROMs) were used as biomarkers for oxidative stress. The preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio were found to be significantly negatively correlated with the serum d-ROM levels at 96 h after surgery, and the rate of increase in serum d-ROM levels between baseline and 96 h postoperatively. This study suggested the preoperative serum EPA + DHA levels and the (EPA + DHA)/AA ratio can be negatively associated with oxidative stress immediately after TKA.

The Influence of Eicosapentaenoic Acid to Arachidonic Acid Ratio on Long-term Cardiovascular Events Following Percutaneous Coronary Intervention.

Objective The relationship between cardiovascular disease and the serum polyunsaturated fatty acid parameters has been reported. The aim of the present study was to investigate the association between the eicosapentaenoic acid and arachidonic acid (EPA/AA) ratio and long-term cardiovascular events in patients with coronary artery disease. Methods We identified a total of 831 patients who underwent percutaneous coronary intervention and whose EPA/AA ratio was available. The patients were divided into two groups according to their serum EPA/AA ratio (median, 0.29; interquartile range 0.19-0.47): those in the lower quartile of EPA/AA ratios (Low EPA/AA group; n=231) and all other subjects (High EPA/AA group; n=600). The primary endpoints included a composite of cardiovascular death, myocardial infarction, and ischemic stroke. Results Patients in the Low EPA/AA group were significantly younger (66.0±12.6 years vs. 69.9±9.3 years, p<0.001), current smokers (33.3% vs. 22.7%, p=0.002), and had a history of myocardial infarction (20.3% vs. 12.3%, p=0.003). During the follow-up (median, 1,206 days; interquartile range, 654-1,910 days), the occurrence of the primary endpoint was significantly higher in the Low EPA/AA group than in the High EPA/AA group. Of note, the rate of cardiovascular death was significantly higher in the Low EPA/AA group, and the rates of myocardial infarction and stroke tended to be higher. Conclusion A low EPA/AA ratio was associated with long-term adverse cardiovascular events in Japanese patients with coronary artery disease.

EPA’s pleiotropic mechanisms of action: a narrative review

ABSTRACT Treatment with icosapent ethyl 4 g/day, a highly purified and stable ethyl ester of eicosapentaenoic acid (EPA), demonstrated a significant reduction in atherosclerotic cardiovascular disease (ASCVD) events and death in REDUCE-IT. However, analyses of REDUCE-IT and meta-analyses have suggested that this clinical benefit is greater than can be achieved by triglyceride reduction alone. EPA therefore may have additional pleiotropic effects, including anti-inflammatory and anti-aggregatory mechanisms. EPA competes with arachidonic acid for cyclooxygenase and lipoxygenase, producing anti-inflammatory and anti-aggregatory metabolites rather than the more deleterious metabolites associated with arachidonic acid. Changing the EPA:arachidonic acid ratio may shift metabolic status from pro-inflammatory/pro-aggregatory to anti-inflammatory/anti-aggregatory. EPA also has antioxidant effects and increases synthesis of nitric oxide. Incorporation of EPA into phospholipid bilayers influences membrane structure and may help to prevent cardiac arrhythmias. Clinically, this may translate into improved vascular health, including regression of atherosclerotic plaque. Overall, EPA has a range of pleiotropic effects that contribute to a reduction in ASCVD.

Changes in Serum, Red Blood Cell, and Colonic Fatty Acids in a Personalized Omega-3 Fatty Acid Supplementation Trial

This study evaluated changes in fatty acids from sera, red blood cells, and colonic biopsies from a phase Ib clinical trial of personalized ω-3 fatty acid dosing in 47 healthy volunteers. The trial aimed to reduce colonic prostaglandin E2 (PGE2), a pro-inflammatory product of arachidonic acid (AA) oxidation. The personalized doses ranged 2–10 grams/day (54% eicosapentaenoic acid, EPA, 24% other ω-3 fatty acids). In colon, increases in ω-3 highly unsaturated fatty acids (HUFA) and EPA:AA ratios each were correlated with decreases in PGE2. Changes in either colonic EPA:AA ratios or ω-3 HUFA were significantly correlated with changes in the same fatty acid measures in red blood cells or serum. The only blood-based measure significantly correlated with changes in colonic PGE2 was change in red blood cell ω-3 HUFA (ρ = −0.39), and the increase in red blood cell ω-3 HUFA was significantly greater in participants who had at least a median reduction in colonic PGE2 vs. those who did not. In summary, fatty acid changes in blood did reflect fatty acid changes in the colon, but additional factors will be needed for optimizing dosing models that seek to predict the anti-inflammatory effects of ω-3 fatty acids on the colon.

Effects of compound-326, a selective delta-5 desaturase inhibitor, in ApoE knockout mice with two different protocols for atherosclerosis development.

We previously confirmed its anti-atherosclerotic effects by pre-treatment with compound-326, a selective delta-5 desaturase (D5D) inhibitor, in Western diet-fed ApoE knockout mice. In the present study, we evaluated effects of compound-326 in ApoE knockout mice with two different protocols for atherosclerosis development. In a post-treatment protocol, where the compound treatment started after 10 weeks pre-feeding of Western diet, compound-326 (1 and 3 mg/kg/day, p.o. for 12 weeks) significantly reduced the atherosclerotic lesion area in the aorta (24% reduction at 3 mg/kg/day). In another protocol using Paigen diet (containing 12.5% cholesterol and 5% sodium cholate), compound-326 (3 and 10 mg/kg/day, p.o. for 7 weeks) also significantly reduced the lesion area (36% reduction at 3 mg/kg/day). In both protocols, Compound-326 significantly reduced the hepatic ratio of arachidonic acid to dihomo-γ-linolenic acid, blood inflammatory eicosanoid production and plasma soluble intercellular adhesion molecule 1 (sICAM-1) levels, similarly to the previous pre-treatment study. Compound-326 exerted anti-atherosclerotic effects in ApoE knockout mice with the two different protocols for atherosclerosis development further supporting D5D inhibition as a promising strategy in treating atherosclerosis.