Omega-3 Eicosapentaenoic Acid Research Articles

Characterization of a novel strain of Tribonema minus demonstrating high biomass productivity in outdoor raceway ponds

Photosynthetic algae represent a large, diverse bioresource potential. Yellow-green algae of the genus Tribonema are candidates for production of biofuels and other bioproducts. We report on a filamentous isolate from an outdoor raceway polyculture growing on municipal reclaimed wastewater which we classified as T. minus. Over one year of cultivation in 3.5m2 raceway ponds fed by reclaimed municipal wastewater, T. minus cultures were more productive than the native algal polycultures, with annual average productivities of 15.9±0.3 and 13.4±0.4g/m2/day, respectively. The biochemical composition of T. minus biomass grown outdoors was constant year-round, with 28.3±0.4% carbohydrates, 37.6±0.7% proteins, and 6.1±0.3% fatty acids (measured as methyl esters), with up to 4.0% of the valuable omega-3 eicosapentaenoic acid, on an ash-free dry-weight basis. In summary, T. minus was more productive, easier to harvest and produced higher quality biomass than the native polycultures.

Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation

Atrial fibrillation (AF) is the most common heart rhythm disturbance, continues to increase in incidence, and results in significant morbidity and mortality. The marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D have been reported to have both benefits and risks with respect to incident AF, but large-scale, long-term randomized trial data are lacking. To test the effects of long-term administration of marine omega-3 fatty acids and vitamin D on incident AF. An ancillary study of a 2 × 2 factorial randomized clinical trial involving 25 119 women and men aged 50 years or older without prior cardiovascular disease, cancer, or AF. Participants were recruited directly by mail between November 2011 and March 2014 from all 50 US states and were followed up until December 31, 2017. Participants were randomized to receive EPA-DHA (460 mg/d of EPA and 380 mg/d of DHA) and vitamin D3 (2000 IU/d) (n = 6272 analyzed); EPA-DHA and placebo (n = 6270 analyzed); vitamin D3 and placebo (n = 6281 analyzed); or 2 placebos (n = 6296 analyzed). The primary outcome was incident AF confirmed by medical record review. Among the 25 119 participants who were randomized and included in the analysis (mean age, 66.7 years; 50.8% women), 24 127 (96.1%) completed the trial. Over a median 5.3 years of treatment and follow-up, the primary end point of incident AF occurred in 900 participants (3.6% of study population). For the EPA-DHA vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.24; P = .19). For the vitamin D3 vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.25; P = .19). There was no evidence for interaction between the 2 study agents (P = .39). Among adults aged 50 years or older, treatment with EPA-DHA or vitamin D3, compared with placebo, resulted in no significant difference in the risk of incident AF over a median follow-up of more than 5 years. The findings do not support the use of either agent for the primary prevention of incident AF. ClinicalTrials.gov Identifiers: NCT02178410; NCT01169259.

Omega-3 Eicosapentaenoic Acid Reduces Prostate Tumor Vascularity.

The impact of omega (ω)-3 fatty acids on prostate cancer is controversial in epidemiological studies but experimental studies suggest a protective effect. However, little is known about the mechanism of action. Here, we studied the effects of purified fatty acid molecules on prostate tumor progression using the TRAMP-C2 syngeneic immunocompetent mouse model. Compared with ω-6 or ω-9-supplemented animals, we observed that late-stage prostate tumor growth was reduced with a monoacylglyceride (MAG)-conjugated form of eicosapentaenoic acid (EPA) supplementation, whereas docosahexanenoic acid (DHA) caused an early reduction. MAG-EPA significantly decreased tumor blood vessel diameter (P < 0.001). RNA sequencing analysis revealed that MAG-EPA downregulated angiogenesis- and vascular-related pathways in tumors. We also observed this tissue vascular phenotype in a clinical trial testing MAG-EPA versus a high oleic sunflower oil placebo. Using anti-CD31 IHC, we observed that MAG-EPA reduced blood vessel diameter in prostate tumor tissue (P = 0.03) but not in normal adjacent tissue. Finally, testing autocrine and paracrine effects in an avascular tumor spheroid growth assay, both exogenous MAG-EPA and endogenous ω3 reduced VEGF secretion and in vitro endothelial cell tube formation and blocked tumor spheroid growth, suggesting that ω3 molecules can directly hinder prostate cancer cell growth. Altogether, our results suggest that fatty acids regulate prostate cancer growth and that a tumor-specific microenvironment is required for the anti-vascular effect of MAG-EPA in patients with prostate cancer. IMPLICATIONS: Increasing the amount of ingested EPA omega-3 subtype for patients with prostate cancer might help to reduce prostate tumor progression by reducing tumor vascularization.

Fish Oil Enriched in EPA, but Not in DHA, Reverses the Metabolic Syndrome and Adipocyte Dysfunction Induced by a High-Fat Diet

This study aimed to investigate the effects of two commercially available fish oils (FOs) containing different proportions of two omega-3 fatty acids (FA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the metabolic and endocrine dysfunctions of white adipose tissue resulting from obesity. Male C57BL/6J mice, 8 weeks old, received a control or high-fat diet (CO and HF groups, with 9% and 59% energy from fat, respectively) for 8 weeks. The next 8 weeks, the HF group was subdivided into HF, HF+FO/E (HF+5:1 EPA:DHA), and HF+FO/D (HF+5:1 DHA:EPA). Supplementation was performed by gavage, three times a week. All groups that received the HF diet had lower food and caloric intake, but a higher fat intake, body weight (BW) gain, glucose intolerance, and a significant increase in inguinal (ING), retroperitoneal (RP), and epididymal (EPI) adipose tissues when compared to the CO group. Additionally, HF and HF+FO/D groups showed insulin resistance, adipocyte hypertrophy, increased lipolysis and secretion of TNF-α, resistin and IL-10 adipokines by ING and RP adipocytes, and adiponectin only by the HF+FO/D group in ING adipocytes. All of these effects were completely reversed in the HF+FO/E group, which also showed partial reversion in BW gain and glucose intolerance. Both the HF+FO/E and HF+FO/D groups showed a reduction in ING and RP adipose depots when compared to the HF group, but only HF+FO/E in the EPI depot. HF+FO/E, but not HF+FO/D, was able to prevent the changes triggered by obesity in TNF-α, Il-10, and resistin secretion in ING and RP depots. These results strongly suggest that different EPA:DHA ratios have different impacts on the adipose tissue metabolism, FO being rich in EPA, but not in DHA, and effective in reversing the changes induced by obesity.

The placental lipidome of maternal antenatal depression predicts socio-emotional problems in the offspring

While maternal mental health strongly influences neurodevelopment and health in the offspring, little is known about the determinants of inter-individual variation in the mental health of mothers. Likewise, the in utero biological pathways by which variation in maternal mental health affects offspring development remain to be defined. Previous studies implicate lipids, consistent with a known influence on cognitive and emotional function, but the relevance for maternal mental health and offspring neurodevelopment is unclear. This study characterizes the placental and circulatory lipids in antenatal depression, as well as socio-emotional outcomes in the offspring. Targeted liquid chromatography-mass spectrometry covering 470 lipid species was performed on placenta from 186 women with low (n = 70) or high (n = 116) levels of antenatal depressive symptoms assessed using the Edinburgh Postnatal Depression Scale at 26 weeks’ gestation. Child socio-emotional outcomes were assessed from the Child Behavior Check List (CBCL) at 48 months. Seventeen placental lipid species showed an inverse association with antenatal EPDS scores. Specifically, lower levels of phospholipids containing LC-PUFAs: omega-3 docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and omega-6 arachidonic acid (AA) were significantly associated with depressive symptoms. Additional measurement of LC-PUFA in antenatal plasma samples at mid-gestation confirmed the reduced circulation of these specific fatty acids in mothers. Reduced concentration of the placental phospholipids also predicted poorer socio-emotional outcomes in the offspring. This study provides new insights into the role of the materno-fetal lipid cross-talk as a mechanism linking maternal mental health to that of the offspring. These findings show the potential utility of nutritional approaches among pregnant women with depressive symptoms to reduce offspring risk for later socio-emotional problems.

The Influence of Long-Chain Omega-3 Fatty Acids on Eccentric Exercise-Induced Delayed Muscle Soreness: Reported Outcomes Are Compromised by Study Design Issues.

Delayed onset muscle soreness (DOMS) following eccentric exercise is associated with increased inflammation which can be debilitating. Incorporation of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA), eicosapentaenoic acid, and docosahexaenoic acid into membrane phospholipids provides anti-inflammatory, proresolving, and analgesic effects. This systematic review aims to examine both the quality of studies and the evidence for LC n-3 PUFA in the attenuation of DOMS and inflammation following eccentric exercise, both which of course are empirically linked. The Scopus, Embase, and Web of Science electronic databases were searched to identify studies that supplemented fish oil for a duration of ≥7 days, which included DOMS outcomes following an eccentric exercise protocol. Fifteen (n = 15) studies met inclusion criteria. Eccentric exercise protocols varied from single to multijoint activities. Risk of bias, assessed using either the Cochrane Collaboration tool or the Risk of Bias in Nonrandomized Studies of Interventions tool, was judged as "unclear" or "medium," respectively, for the majority of outcomes. Furthermore, a custom 5-point quality assessment scale demonstrated that only one (n = 1) study satisfied current recommendations for investigating LC n-3 PUFA. In combination, this highlights widespread inappropriate design protocols among studies investigating the role of LC n-3 PUFA in eccentric exercise. Notwithstanding these issues, LC n-3 PUFA supplementation appears to have favorable effects on eccentric exercise-induced DOMS and inflammatory markers. However, the optimal LC n-3 PUFA supplemental dose, duration, and fatty acid composition will only become clear when study design issues are rectified and underpinned by appropriate hypotheses.

Nutritional consequences of breeding away from riparian habitats in Bank Swallows: new evidence from multiple endogenous markers.

The Bank Swallow (Riparia riparia), a threatened species in Canada, breeds primarily in banks at lakeshores and rivers and in artificial (typically inland) aggregate mining pits. Inland pits may be ecological traps for this species, but relative dietary trade-offs between these two nesting habitats have not been investigated. The availability of aquatic emergent insects at lakeshores may have associated nutritional benefits for growing nestlings due to increased omega-3 fatty acids (FAs) in prey. We compared the diets of juvenile swallows from lakeshore and inland pit sites using assays of stable isotope values (δ13C, δ15N, δ2H) of feathers, faecal DNA metabarcoding and blood plasma FAs. Colony proximity to Lake Erie influenced the use of aquatic versus terrestrial insects by Bank Swallow adults and juveniles. Feather δ2H was particularly useful as a tracer of aquatic emergent versus terrestrial prey, and inland juveniles had feathers enriched in 2H, reflective of diets composed of fewer aquatic emergent insects. DNA metabarcoding of juvenile and adult faecal material indicated that lakeshore birds consumed more aquatic-emergent chironomids than inland birds. Lakeshore juveniles had elevated plasma omega-3 eicosapentaenoic acid levels compared with inland pit-breeding birds. We discuss the need to consider 'nutritional landscapes' and the importance of this concept in conservation of declining species and populations.

Changes in bioactive lipid mediators in response to short-term exposure to ambient air particulate matter: A targeted lipidomic analysis of oxylipin signaling pathways

Exposure to ambient air particulate matter (PM) is a risk factor for cardiometabolic diseases. The knowledge of the underlying mechanisms is still evolving, but systemic inflammation and oxidative stress are central to the ability of PM to induce cardiometabolic effects. Oxylipins derived from polyunsaturated fatty acids (PUFAs) are bioactive lipid mediators that have fundamental roles in the signaling of inflammatory events. However, the associations between oxylipins and short-term exposure to PM in humans are unknown. Using targeted lipidomic analyses, we measured 16 oxylipins derived from lipoxygenase (LOX), cytochrome P450 (CYP), and cyclooxygenase (COX) pathways and their parent PUFAs in serum samples of 110 adults enrolled in a panel study in Beijing, China. Each participant completed 2-7 clinical visits from 2013 to 2015. PM with aerodynamic diameter≤2.5μm (PM2.5) and≤0.1μm (ultrafine particles, UFPs) were continuously monitored at a station. Linear mixed-effects models were applied to examine the associations between changes in lipid mediators and exposure to ambient PM during the preceding 1 to 3days before the clinical visit. Serum concentrations of PUFAs, including omega-6 arachidonic acid (ARA) and omega-3 eicosapentaenoic acid (EPA), were significantly increased in association with interquartile range (IQR) increases in PM with different exposure windows (i.e., 1-3days). Regarding oxylipins, significant PM-associated changes included increases in LOX-derived leukotriene B4 (LTB4), 12(S)-, 15(S)-hydroxyeicosatetraenoic acid (HETE), 12-hydroxyeicosapentaenoic acid (HEPE), and 17-hydroxydocosahexaenoic acid (HDHA); an increase in CYP-derived 5,6-dihydroxyeicosatrienoic acid (DHET); and a decrease in COX-derived prostaglandin E2. Short-term exposure to PM was associated with PUFAs and oxylipins derived from LOX, CYP, and COX pathways in humans. Our findings provide mechanistic insight suggesting bioactive oxylipins might be used as biomarkers and have important implications as mediators of PM-associated systemic cardiometabolic effects.

Omega-3 Eicosapentaenoic Acid Is Related to Happiness and a Sense of Fulfillment-A Study among Female Nursing Workers.

Background: Omega (ω) 3 fatty acid (FA) is a polyunsaturated FA (PUFA) that can modulate some mental statuses. However, most studies have not considered the functional differences between eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We investigated associations among happiness, a sense of fulfillment and serum ω3 PUFA levels. Methods: Participants were 133 female staff from a hospital and nursing homes. Happiness was measured using the Japanese version of the subjective happiness scale (SHS); a sense of fulfillment was assessed using a visual analogue scale. Serum FA concentrations were measured. A partial correlation test and a regression model were applied. Results: The SHS scores showed significantly positive correlations with a sense of fulfillment, DHA% and EPA% (p < 0.05, < 0.05 and < 0.005, respectively), after controlling for age, BMI, menopause, snacking habits and leisure-time physical activities. A sense of fulfillment was significantly negatively correlated with α-linoleic acid%, and positively correlated with DHA% and EPA% (p < 0.05, < 0.05 and < 0.005, respectively), after controlling for the confounders. A regression model showed that a sense of fulfillment, EPA, and not stopping menstruation explained happiness (standardised beta, B = 0.18, p < 0.05; B = 0.24, p < 0.01; and B = 0.32, and p < 0.05, respectively), whereas age, BMI and snacking habits could not. Simultaneously, a regression model could not explain the association between DHA and happiness. Conclusion: Happiness was related with serum EPA%, a sense of fulfillment, and premenopause.

A step to shell biorefinery—Extraction of astaxanthin-rich oil, protein, chitin, and chitosan from shrimp processing waste

Management of waste generated in fish processing industries is of great concern worldwide. Shrimp processing waste can be used for the generation of various biobased products along with its remediation. The present work was carried out to valorize shrimp processing waste using biorefinery approach. Ridgeback shrimp (Solenocera choprai) waste was used to produce commercially important biomolecules such as astaxanthin-rich oil, protein, chitin, and chitosan. Supercritical carbon dioxide extraction was performed for the extraction of astaxanthin and oil. Astaxanthin yield using super critical fluid extraction method was 30.26 ± 0.06 mg/kg dry shell weight. Extracted oil was found to have high content of health promoting polyunsaturated fatty acids, in particular omega-3 fatty acids, viz, eicosapentaenoic acid and docosahexaenoic acid. The remaining waste after the supercritical fluid extraction was used for protein extraction and the recovery yield was found to be 22.25 ± 0.15%. The residue left after extraction of astaxanthin and protein was used to extract chitin and the extracted chitin was used to produce chitosan. The yield of chitin and chitosan was 224.36 ± 0.32 g/kg and 156.99 ± 0.16 g/kg, respectively. The significant findings of the study suggest the potential of biorefinery in utilizing shrimp processing waste to produce commercially important products.

Lipid class and fatty acid composition of oil extracted from Atlantic salmon by-products under different optimization parameters of enzymatic hydrolysis

Abstract Six operational parameters, including fish part, antioxidant use, water addition, enzyme types, enzyme concentration and hydrolysis time, were studied about their effect on nutritional composition of oil enzymatically extracted from farmed Atlantic salmon by-products. Compared to the oil extracted from salmon viscera, the oil extracted from mixture of salmon heads and frames had higher amounts of triacylglycerols (TAGs), omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and lower amounts of omega-6 PUFAs. The interaction between water and high levels of hydrolysis time (4 h) or enzyme concentration (1%) resulted in decreased TAG content, increased content of phospholipids (PLs) and increased omega-6 PUFA content. The addition of antioxidant significantly increased the average content of omega-6 PUFAs, but decreased EPA and DHA amounts in viscera oil due to the pro-antioxidant activity of ascorbic acid. The use of Alcalase, Flavourzyme or SEBPRo didn't result in any significant difference in oil composition under studied conditions. The negative correlation between amounts of TAG and free fatty acid (FFA) indicates that the increase of FFA content resulted in the decrease of TAG content, mainly due to the oxidation of TAG promoted by FFAs.

340P Omega-3 fatty acids for cancer cachexia in advanced non-small cell lung cancer: A meta-analysis

Cancer cachexia is a common debilitating weight loss syndrome in advanced cancer, particularly in lung cancer patients. The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), because of their immune-modulating effects, have been used to improve the nutritional status of patients with cancer cachexia. This meta-analysis evaluated the effect of omega-3 fatty acids in change in weight and lean body mass or skeletal mass, and in health-related quality of life (HRQoL) scores in patients with advanced non-small cell lung cancer. Electronic databases were extensively searched for randomized controlled trials investigating omega-3 fatty acids in cancer cachexia among patients with advanced non-small cell lung cancer. Unpublished literature was also searched through manual handsearching and accessing online databases. Two review authors independently evaluated the methodological quality of the trials and analyzed the data. Six trials (394 patients) were included in the analysis. Five trials assessed change in weight, while two trials assessed change in lean body mass or skeletal mass, and HRQoL scores (Global Health and Physical Functioning Subscales). There is a significant difference in change in weight (mean difference [MD]: 1.22, 95% CI: 1.05 to 1.38; ƶ: 14.49, p<0.01) and HRQoL scores (Global Health subscale [MD: 14.40, 95% CI: 9.22 to 19.59, ƶ: 5.44, p<0.01] and Physical Functioning subscale [MD: 10.38, 95% CI: 8.50 to 12.27, ƶ: 10.78, p<0.01]) favoring the omega-3 fatty acids group. However, there is no sufficient evidence to support the association of change in lean body mass or skeletal mass, and the said intervention (MD: 2.05, 95% CI: -0.55 to 4.66; ƶ: 1.54, p: 0.12). Among patients with advanced non-small lung cancer with cancer cachexia, there is a significant increase in weight and HRQoL scores in the omega-3 fatty acids group. However, there is no sufficient evidence to support the association of change in lean body mass or skeletal mass, and the said intervention.

Circulating Omega-3 Fatty Acids and Incident Adverse Events in Patients With Acute Myocardial Infarction

Dietary omega-3 eicosapentaenoic acid (EPA) has multiple cardioprotective properties. The proportion of EPA in serum phosphatidylcholine (PC) mirrors dietary EPA intake during previous weeks. Circulating EPA in ST-segment elevation myocardial infarction (STEMI) relates to smaller infarct size and preserved long-term ventricular function. The authors investigated whether serum-PC EPA (proxy for marine omega-3 consumption) levels at the time of STEMI were associated with a lower incidence of major adverse cardiovascular events (MACE), all-cause mortality, and readmission for cardiovascular (CV) causes at 3 years' follow-up. We also explored the association of alpha-linolenic acid (ALA, proxy for vegetable omega-3 intake) with all-cause mortality and MACE. The authors prospectively included 944 consecutive patients with STEMI (mean age 61 years, 209 women) undergoing primary percutaneous coronary intervention. We determined serum-PC fatty acids with gas chromatography. During follow-up, 211 patients had MACE, 108 died, and 130 were readmitted for CV causes. A Cox proportional hazards model adjusted for known clinical predictors showed that serum-PC EPA at the time of STEMI was inversely associated with both incident MACE and CV readmission (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62 to 0.94, and HR: 0.74; 95%CI: 0.58 to 0.95, respectively, for a 1-standard deviation [SD] increase). Serum-PC ALA was inversely related to all-cause mortality (HR: 0.65; 95%CI: 0.44 to 0.96, for a 1-SD increase). Elevated serum-PC EPA and ALA levels at the time of STEMI were associated with a lower risk of clinical adverse events. Consumption of foods rich in these fatty acids might improve the prognosis of STEMI.

The Fatty Acid Composition of Human Follicular Fluid Is Altered by a 6‐Week Dietary Intervention That Includes Marine Omega‐3 Fatty Acids

The fatty acid composition of human follicular fluid is important for oocyte development and for pregnancy following in vitro fertilization (IVF). This study investigated whether a dietary intervention that included an increase in marine omega-3 fatty acids, olive oil and vitamin D alters the fatty acid composition of human follicular fluid. The association of lifestyle factors with follicular fluid fatty acid composition was also investigated. Fifty-five couples awaiting IVF were randomized to receive the 6-week treatment intervention of olive oil for cooking, an olive oil-based spread, and a daily supplement drink enriched with vitamin D and the marine omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and 56 couples were randomized to receive placebo equivalents. Dietary questionnaires were completed, and samples of blood were taken before and after the intervention. Follicular fluid was collected at oocyte retrieval and the fatty acid profile assessed using gas chromatography. In the control group, individual fatty acids in red blood cells and follicular fluid were significantly correlated. Furthermore, a healthier diet was associated with a lower percentage of follicular fluid arachidonic acid. The follicular fluid of women in the treatment group contained significantly higher amounts of EPA and DHA compared to the control group, while the omega-6 fatty acids linoleic, γ-linolenic, dihomo-γ-linolenic, and arachidonic were lower. This is the first report of a dietary intervention altering the fatty acid composition of follicular fluid in humans. Further research is required to determine whether this intervention improves oocyte quality.

The fish-oil paradox.

Increasing interest has focused on the potential cardioprotective effects of the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the basis of findings from epidemiology and cohort studies. This review will summarize the findings of contemporary clinical trials of omega-3 fatty acids. Although a large clinical trial performed prior to the widespread use of statins demonstrated cardiovascular benefit with fish oils, subsequent studies have failed to reproduce this result. More recent studies have demonstrated a reduction in cardiovascular risk with administration of high-dose EPA, but not a carboxylic acid formulation containing both EPA and DHA or with lower doses of omega-3 fatty acids. Administration of omega-3 fatty acids differing in either composition or dose produce variable effects on cardiovascular outcomes. This has implications for both the public health and pharmacological approach to cardiovascular prevention.

Plasma Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Brown Adipose Tissue Activity in Humans.

Brown adipose tissue (BAT) activation is a possible therapeutic strategy to increase energy expenditure and improve metabolic homeostasis in obesity. Recent studies have revealed novel interactions between BAT and circulating lipid species—in particular, the non-esterified fatty acid (NEFA) and oxylipin lipid classes. This study aimed to identify individual lipid species that may be associated with cold-stimulated BAT activity in humans. A panel of 44 NEFA and 41 oxylipin species were measured using mass-spectrometry-based lipidomics in the plasma of fourteen healthy male participants before and after 90 min of mild cold exposure. Lipid measures were correlated with BAT activity measured via 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), along with norepinephrine (NE) concentration (a surrogate marker of sympathetic activity). The study identified a significant increase in total NEFA concentration following cold exposure that was positively associated with NE concentration change. Individually, 33 NEFA and 11 oxylipin species increased significantly in response to cold exposure. The concentration of the omega-3 NEFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at baseline was significantly associated with BAT activity, and the cold-induced change in 18 NEFA species was significantly associated with BAT activity. No significant associations were identified between BAT activity and oxylipins.

The efficacy of bortezomib in human multiple myeloma cells is enhanced by combination with omega-3 fatty acids DHA and EPA: Timing is essential

Although bortezomib as one of the first line medicines that has greatly improved the overall survival of patients with multiple myeloma (MM), undesired drug resistance is frequently observed. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been shown to be able to enhance the efficacy of chemotherapeutic drugs in many cancer types. The aim of the present study was to further evaluate the anticancer activity of DHA and EPA in relation to bortezomib chemosensitivity in human MM cells. The potential involvement of NF-κB signaling pathway was studied. MM cells were treated with DHA/EPA with or without bortezomib. Cell viability was estimated by WST-1 assay. Apoptotic cells were determined through flow cytometry using annexin V and propidium iodide (PI) staining. Protein expression and phosphorylation was investigated by western blotting. Cell type dependent anticancer potential of DHA and EPA was observed in the cell viability assay. DHA and EPA induced apoptosis in L363, OPM2, MM.1S and U266cell lines through both mitochondrial and death receptor pathways. Treating MM cells with DHA and EPA significantly downregulated IκBα and upregulated phosphorylation of p65, indicating that they triggered NF-κB activation in MM cells. Treating cells with DHA or EPA prior to bortezomib enhanced the induced cell death. However, concomitant use of bortezomib in combination with either of DHA or EPA decreased the cell death induced by bortezomib, indicating that timing of coincubation is important for the effects on chemosensitivity. The present study provides novel evidence for the anticancer effects of DHA and EPA, and highlights their rational utilization in combination with bortezomib to achieve improved therapeutic outcome for MM.

Antimicrobial Activity of EPA and DHA against Oral Pathogenic Bacteria Using an In Vitro Multi-Species Subgingival Biofilm Model.

In search for natural products with antimicrobial properties for use in the prevention and treatment of periodontitis, the purpose of this investigation was to evaluate the antimicrobial activity of two omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), using an in vitro multi-species subgingival biofilm model including Streptococcus oralis, Actinomyces naeslundii, Veillonella parvula, Fusobacterium nucleatum, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The antimicrobial activities of EPA and DHA extracts (100 µM) and the respective controls were assessed on 72 h biofilms by their submersion onto discs for 60 s. Antimicrobial activity was evaluated by quantitative polymerase chain reaction (qPCR), confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). ANOVA with Bonferroni correction was used to evaluate the antimicrobial activity of each of the fatty acids. Both DHA and EPA significantly reduced (p < 0.001 in all cases) the bacterial strains used in this biofilm model. The results with CLSM were consistent with those reported with qPCR. Structural damage was evidenced by SEM in some of the observed bacteria. It was concluded that both DHA and EPA have significant antimicrobial activity against the six bacterial species included in this biofilm model.

Impact of omega-3 fatty acid DHA and EPA supplementation in pregnant or breast-feeding women on cognitive performance of children: systematic review and meta-analysis.

The omega-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are important for brain development and cognitive performance. Because they are semi-essential fatty acids, they must be obtained from food. However, the dietary reference intakes of DHA and EPA have not yet been established. In women, a low DHA and/or EPA serum level during pregnancy or breastfeeding might negatively affect their children. For this study, we conducted a systematic review and meta-analysis of randomized control trials on the association between the consumption of fish oil supplements in pregnant and/or breastfeeding women and the cognitive performance of their children. The PubMed, Embase, and Central literature databases were systematically searched. We included and extracted relevant studies in duplicate and assessed study quality. Cognitive outcomes were grouped according to published criteria and according to time elapsed after the intervention. We performed fixed-effects meta-analyses for each cognitive outcome and for birth weight. We assessed potential confounding with meta-regressions and sensitivity analyses. A total of 11 trials were included. No significant association was found between DHA/EPA supplementation and any of the assessed cognitive parameters or birth weight. Our results confirm previous reviews on the studied topic. Reasons for inconclusive results may be small sample sizes for each assessed category, questionable quality of included studies, and the difficulty of reliably measuring cognitive performance in small children. Blood levels of omega-3 long-chain polyunsaturated fatty acids were mostly not comparable. Furthermore, the influence of genetic and environmental factors could not be assessed. Studies in this field should address such shortcomings.

Hepatic Levels of DHA-Containing Phospholipids Instruct SREBP1-Mediated Synthesis and Systemic Delivery of Polyunsaturated Fatty Acids.

SummaryPolyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA) and arachidonic acid (ARA), play fundamental roles in mammalian physiology. Although PUFA imbalance causes various disorders, mechanisms of the regulation of their systemic levels are poorly understood. Here, we report that hepatic DHA-containing phospholipids (DHA-PLs) determine the systemic levels of PUFAs through the SREBP1-mediated transcriptional program. We demonstrated that liver-specific deletion of Agpat3 leads to a decrease of DHA-PLs and a compensatory increase of ARA-PLs not only in the liver but also in other tissues including the brain. Together with recent findings that plasma lysophosphatidylcholine (lysoPC) is the major source of brain DHA, our results indicate that hepatic AGPAT3 contributes to brain DHA accumulation by supplying DHA-PLs as precursors of DHA-lysoPC. Furthermore, dietary fish oil-mediated suppression of hepatic PUFA biosynthetic program was blunted in liver-specific Agpat3 deletion. Our findings highlight the central role of hepatic DHA-PLs as the molecular rheostat for systemic homeostasis of PUFAs.