Especially Eicosapentaenoic Acid Research Articles

Delta-5 elongase knockout reduces docosahexaenoic acid and lipid synthesis and increases heat sensitivity in a diatom.

Recent global marine lipidomic analysis reveals a strong relationship between ocean temperature and phytoplanktonic abundance of omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are essential for human nutrition and primarily sourced from phytoplankton in marine food webs. In phytoplanktonic organisms, EPA may play a major role in regulating the phase transition temperature of membranes, while the function of DHA remains unexplored. In the oleaginous diatom Phaeodactylum tricornutum, DHA is distributed mainly on extraplastidial phospholipids, which is very different from the EPA enriched in thylakoid lipids. Here, CRISPR/Cas9-mediated knockout of delta-5 elongase (ptELO5a), which encodes a delta-5 elongase (ELO5) catalyzing the elongation of EPA to synthesize DHA, led to a substantial interruption of DHA synthesis in P. tricornutum. The ptELO5a mutants showed some alterations in transcriptome and glycerolipidomes, including membrane lipids and triacylglycerols under normal temperature (22°C), and were more sensitive to elevated temperature (28°C) than wild type. We conclude that PtELO5a-mediated synthesis of small amounts of DHA has indispensable functions in regulating membrane lipids, indirectly contributing to storage lipid accumulation, and maintaining thermomorphogenesis in P. tricornutum. This study also highlights the significance of DHA synthesis and lipid composition for environmental adaptation of P. tricornutum.

Molecular Mechanisms Associated with the Inhibitory Role of Long Chain n-3 PUFA in Colorectal Cancer.

Colorectal cancer (CRC) is the third leading cause of cancer-related death in the world. Multiple evidence suggests that there is an association between excess fat consumption and the risk of CRC. The long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential for human health, and both in vitro and in vivo studies have shown that these fatty acids can prevent CRC development through various molecular mechanisms. These include the modulation of arachidonic acid (AA) derived prostaglandin synthesis, alteration of growth signaling pathways, arrest of the cell cycle, induction of cell apoptosis, suppression of angiogenesis and modulation of inflammatory response. Human clinical studies found that LC n-3 PUFA combined with chemotherapeutic agents can improve the efficacy of treatment and reduce the dosage of chemotherapy and associated side effects. In this review, we discuss comprehensively the anti-cancer effects of LC n-3 PUFA on CRC, with a main focus on the underlying molecular mechanisms.

Health Benefits of Oily Fish: Illustrated with Blue Shark (Prionace glauca), Shortfin Mako Shark (Isurus oxyrinchus), and Swordfish (Xiphias gladius)

Oily fish is a rich source of energy, proteins, essential amino acids, lipids, vitamins, and minerals. Among the macronutrients with the highest contribution are lipids, mainly long-chain omega 3 polyunsaturated fatty acids (ω-3 LC-PUFA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Both EPA and DHA play a beneficial role in promoting health and preventing many diseases, including cardiovascular diseases, such as stroke and acute myocardial infarction. They also contribute to the prevention of neurological, metabolic, and immune-system-related diseases, as well as supporting body-weight control. Oily fish consumption is also important at different stages of human life, from conception to old age. For example, DHA plays an important role in brain and retina development during fetal development and in the first two years of life, as it positively influences neurodevelopment, such as visual acuity, and cognitive functions. In contrast with the possible health benefits of the intake of oily fish, the presence of certain chemical pollutants, for example, heavy metals, can be a risk for the health of consumers, mainly in sensitive population groups such as pregnant women and children under 2 years of age. The presence of these pollutants is influenced to a greater extent by fish species, their role in the trophic chain, and their size. However, various studies state that the benefits outweigh the risk of consuming certain species. This review will be focused on the health benefits of the intake of three oily fish species, namely blue shark (Prionace glauca), shortfin mako shark (Isurus oxyrinchus), and swordfish (Xiphias gladius).

Analysis of EPA + DHA and omega3/omega6 ratio in 17 edible wild fish species in Bahrain

Fish are an important part of the Mediterranean diet, which recommends consuming more fish (at least twice a week) than meat (on a monthly basis). Over the past decade there has been a significant promotion of fish intake because of its high-quality protein content, low fat content, and because it is a good source of vitamins and minerals, but overall because it contains large amounts of omega 3 polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The aim of this study is to determine the fatty acid contents of ten edible wild fish species sold at the Bahrain market along with twelve previously studied edible wild fish species in Bahrain to find out the best of them in terms of EPA, DHA, and n-3/n-6 ratio. Ten edible wild fish species in which their fatty acid contents were not previously studied were selected from the Bahrain market. Lipid extraction and fatty acid methylation were performed. Gas chromatography analysis was conducted to determine the fatty acid compositions of the selected fish species. The result showed significant differences (p < 0.05) in the fatty acid compositions among all ten fish species studied. Edible wild fish species from the present study were given numbers (number 1 is the one with the best fatty acid contents, whereas number 17 is the one with poorest fatty acid contents) based on the sum of EPA and DHA and the n-3/n-6 ratio. The number one fish based on EPA + DHA was Doubleber Bream (Faskir) 26.63 ± 0.30%, while the lowest sum of EPA + DHA was observed in White Sardinella (Oom) 5.45 ± 0.35%. On the other hand, fish with the highest n-3/n-6 ratio is Doubleber Bream (Faskir) with a ratio of 2.62 ± 0.29%, whereas Haffara Bream (Gorgofan) has the lowest ratio 0.60 ± 1.45%. The sum of EPA and DHA and the n-3/n-6 ratio of the 17 fish species from Bahrain were compared with fish species that have high amounts of omega-3 around the world and fish species from the Arabian Gulf Sea and the Mediterranean Sea based on the sum of EPA + DHA and n-3/n-6 ratio. The result has shown that EPA + DHA and the n-3/n-6 ratio were similar to those from the Arabian Gulf Sea but lower in the fish species in Bahrain compared to the Mediterranean Sea and those with high amounts of omega-3 around the world. In conclusion, consuming only wild fish species from Bahrain will not be adequate to gain the recommended daily consumption of 500-1000 mg EPA + DHA.

Determination of Fatty Acid Profile in Processed Fish and Shellfish Foods.

Seafood products are a crucial dietary source of n-3 polyunsaturated fatty acids (n-3 PUFA), which are essential for human health. However, the presence of these n-3 PUFA may be subject to changes related to different processing methods. The aim of this study was to determine the fatty acid composition, focusing on n-3 PUFA, in different processed fish and shellfish products of both EU and non-EU origin. The products were purchased from supermarkets and ethnic food shops in Messina (Italy). Gas chromatography with a flame-ionization detector (GC-FID) was used for analysis. Based on the fatty acid profile, the atherogenicity index (AI), thrombogenicity index (TI), and flesh lipid quality index (FLQ) were determined: 0.13-1.04 (AI), 0.19-0.89 (TI), and 0.41-29.90 (FLQ). The percentages of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids fell within the following ranges: 13.55-50.48%, 18.91-65.58%, and 13.84-52.73%, respectively. Considering that all samples showed low AI and TI indices and that all processed fish products proved to be a good source of beneficial PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), their consumption is recommended for humans.

The influence of temperature on performance, biological indices, composition, and nutrient retention of juvenile Chinook salmon (Oncorhynchus tshawytscha) reared in freshwater

This study investigated the effects of different temperatures on the performance, composition, and nutrient retention of Chinook salmon reared in freshwater. Individuals (187.6 ± 27.1 g) were distributed into twelve tanks of 8000 L each (155 to 157 fish per tank) at a temperature of 14 °C. The tanks were transitioned from 14 °C (hatchery temperature) to 8, 12, 16, and 20 °C over seven days. Three fish assessments were performed, the first (initial) when the fish were distributed in the tanks, a second (interim) between days 9 and 16 at the start of the experiment, and a third (final) after 41 to 49 days at the target temperature. At the end of the trial, performance parameters, proximate composition, amino acid, and fatty acid composition, and nutrient retention were evaluated. Better growth performance was observed in fish at 16 °C and 20 °C compared to the lower temperatures. Fish at higher temperatures had higher levels of saturated fatty acids (SFA), while at lower temperatures fish had higher levels of n-3 and n-6 polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). A polynomial relationship between nutrient retention and temperature showed that fish from all treatments retained more lipids than proteins, with higher retention of MUFA compared to the other fatty acid classes. Additionally, DHA retention was approximately three times higher than EPA retention. The results showed that 16 to 20 °C was the optimum temperature range for Chinook salmon, and the performance differences were mainly modulated by lipid retention/catabolism.

CRISPR/Cas9-mediated precision integration of fat-1 and fat-2 from Caenorhabditis elegans at long repeated sequence in channel catfish (Ictalurus punctatus) and the impact on n-3 fatty acid level

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential for the development and health of human and animals. However, n-3 PUFAs in human diets, aquaculture and livestock feed are mainly from oily marine fishes. To improve n-3 fatty acid levels in channel catfish (Ictalurus punctatus), we generated transgenic channel catfish carrying codon optimized Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase and fat-2 gene encoding the delta12 fatty acid desaturase using CRISPR/Cas9 technology. We used a special cocktail design of donor plasmid, utilized mixed HDR, MMEJ and NHEJ repair pathways, and targeted long repeated DNA target sequence (LRS) to improve knock-in (KI) efficiency. Our results showed that two donor DNAs precisely inserted into at least four genomic sites. Detectable on-target KI efficiency of fat-1 was 9.1% (55/605), three times higher than that of fat-2, which might due to the smaller size of the donor fat-1. Sanger sequencing results suggested that HDR was the dominant repair pathway using this method, leading to the highest proportion of on-target KI events. Reverse transcription PCR (RT-PCR) and quantitative real-time PCR (qRT-PCR) demonstrated that the fat-1 and fat-2 transgenes had strong expression, and also greatly improved fads6, elovl2 and elovl5 gene expression in liver and muscle tissues of transgenic channel catfish. Fatty acid analysis showed the fat-1-only transgenic channel catfish had the lower levels of 14:0, 16:0, 18:2n-6, total n-6, and the higher levels of DHA, total n-3 and n-3/n-6 ratio than other genotypes including the fat-2-only, co-integration of fat-1 and fat-2, and wild-type control. In particular, DHA, total n-3 and n-3/n-6 ratio were significantly increased by 37%, 19.8% and 25.2%, respectively, in the fat-1-only transgenic fish than that in the wild-type control (P < 0.05). Our fat-1 and fat-2 KI channel catfish hold promise for improving fish nutritional value, reducing fish oil requirement in aquaculture feed, and serving as an alternative source of n-3 PUFAs.

Stream degradation affects aquatic resource subsidies to riparian ground-dwelling spiders

Freshwater systems have undergone drastic alterations during the last century, potentially affecting cross-boundary resource transfers between aquatic and terrestrial ecosystems. One important connection is the export of biomass by emergent aquatic insects containing omega-3 polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA), that is scarce in terrestrial systems. Because of taxon-specific differences in PUFA content and functional traits, the contribution of different insect groups should be considered, in addition to total biomass export. In this context, one important trait is the emergence mode. Stoneflies, in contrast to other aquatic insects, crawl to land to emerge instead of flying directly from the water surface, making them accessible to ground-dwelling predators. Because stoneflies are especially susceptible to environmental change, stream degradation might cause a mismatch of available and required nutrients, particularly for ground-dwelling predators. In this study, we estimated emergent biomass and EPA export along two streams with different levels of habitat degradation. The EPA content in aquatic insects did not differ with different degrees of habitat degradation and total biomass export in spring was with 7.9 ± 9.6 mg m−2 day−1 in the degraded and 7.3 ± 8.5 mg m−2 day−1 in the natural system, also unaffected. However, habitat degradation substantially altered the contribution of crawling emergence to the total export in spring, with no biomass export by stoneflies at the most degraded sites. The EPA content in ground-dwelling spiders was correlated with emergent stonefly biomass, making up only 16.0 ± 6.2 % of total fatty acids at sites with no stonefly emergence, but 27.3 ± 3.0 % at sites with highest stonefly emergence. Because immune function in ground-dwelling spiders has been connected to EPA levels, reduced crawling emergence might impact spider fitness. Functional traits, like emergence mode as well as nutritional quality, should be considered when assessing the effects of stream degradation on adjacent terrestrial ecosystems.

Anti-Obesity and Gut Microbiota Regulation Effects of Phospholipids from the Eggs of Crab, Portunus Trituberculatus, in High Fat Diet-Fed Mice.

There are resourceful phospholipids in the eggs of the crab, Portunus trituberculatus (Pt-PL). However, their components and bioactivities regarding obesity were unclear. Here, we investigated the composition of Pt-PL and their fatty acids. Moreover, its effects on obesity and gut microbiota were also evaluated in high fat diet (HFD)-fed mice. The results showed that Pt-PL contained 12 kinds of phospholipids, mainly including phosphatidylcholine (PC, 32.28%), phosphatidylserine (PS, 26.51%), phosphatidic acid (PA, 19.61%), phosphatidylethanolamine (PE, 8.81%), and phosphatidylinositol (PI, 7.96%). Polyunsaturated fatty acids (PUFAs) predominated in the fatty acids components of Pt-PL, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Animal experiments demonstrated that Pt-PL significantly alleviated body weight gain, adipose gain, hepatic gain, fasting blood glucose, serum insulin, lipid levels in serum and the liver, and systematic inflammation in HFD-fed mice. Furthermore, Pt-PL regulated gut microbiota, especially in a dramatic reduction in the ratio of Firmicutes to Bacteroidetes at phylum level, as well as significant amelioration in their subordinate categories. Pt-PL reduced fecal lipopolysaccharide and total bile acids, and elevated fecal short chain fatty acid (SCFA) concentrations, particularly acetate and butyrate. These findings suggest that Pt-PL possesses anti-obesity effects and can alter gut microbiota owing to the abundance of PUFAs. Therefore, Pt-PL may be developed as an effective food supplement for anti-obesity and regulation of human gut health.

The Microalgae Phaeodactylum tricornutum Is Well Suited as a Food with Positive Effects on the Intestinal Microbiota and the Generation of SCFA: Results from a Pre-Clinical Study.

Microalgae such as Phaeodactylum tricornutum (PT) are a sustainable source of nutrients, especially eicosapentaenoic acid (EPA), fucoxanthin (Fx), and chrysolaminarin (Chrl), the concentrations of which can vary depending on the culture conditions. We generated three types of diets containing either an EPA- and Fx-rich (EPA/Fx) or Chrl-rich microalgae (with 5, 15, or 25% added to the diet) or an isocaloric control diet (CD). These diets were evaluated over 14 days in young C57BL/6J mice for safety and bioavailability, short-chain fatty acid (SCFA) production, and microbiome analysis. Both microalgae diets increased body weight gain dose-dependently compared to the CD. Microalgae-derived EPA was well absorbed, resulting in increased liver and fat tissue levels and a decrease in the n-6:n-3 ratio in liver tissue. Both microalgae diets increased the production of selected SCFA and decreased the Firmicutes/Bacteriodota ratio, whereas the Chrl-rich diet led to an increase in Akkermansia. Doses of up to 4621 mg Chrl, 920 mg EPA, and 231 mg Fx per kg body weight daily were tolerated without adverse effects. This pre-clinical study shows that PT is suitable for mouse feed, with positive effects on microbiota composition and SCFA production, suggesting beneficial effects on gut health.

Media engineering in marine diatom Phaeodactylum tricornutum employing cost-effective substrates for sustainable production of high-value renewables.

Phaeodactylum tricornutum is a marine diatom, rich in omega-3 polyunsaturated fatty acids especially eicosapentaenoic acid (EPA) and brown pigment, that is, fucoxanthin. These high-value renewables (HVRs) have a high commercial and nutritional relevance. In this study, our focus was to enhance the productivities of such renewables by employing media engineering strategy via., photoautotrophic (P1, P2, P3) and mixotrophic (M1, M2, M3, M4) modes of cultivation with varying substrate combinations of carbon (glycerol: 0.1m) and nitrogen (urea: 441mm and/or sodium nitrate: 882mm). Our results demonstrate that mixotrophic [M4] condition supplemented with glycerol (0.1m) and urea (441mm) feed enhanced productivities (mgL-1 day-1 ) as follows: biomass (770.0), total proteins (36.0), total lipids (22.0), total carbohydrates (23.0) with fatty acid methyl esters (9.6), EPA (2.7), and fucoxanthin (1.1), respectively. The overall yield of EPA represents 28% of total fatty acids in the mixotrophic [M4] condition. In conclusion, our improved strategy of feeding urea to a glycerol-supplemented medium defines a new efficient biomass valorization paradigm with cost-effective substrates for the production of HVRs in oleaginous diatoms P. tricornutum.

Dark matters: Contrasting responses of stream biofilm to browning and loss of riparian shading.

Concentrations of terrestrial‐derived dissolved organic carbon (DOC) in freshwater ecosystems have increased consistently, causing freshwater browning. The mechanisms behind browning are complex, but in forestry‐intensive regions browning is accelerated by land drainage. Forestry actions in streamside riparian forests alter canopy shading, which together with browning is expected to exert a complex and largely unpredictable control over key ecosystem functions. We conducted a stream mesocosm experiment with three levels of browning (ambient vs. moderate vs. high, with 2.7 and 5.5‐fold increase, respectively, in absorbance) crossed with two levels of riparian shading (70% light reduction vs. open canopy) to explore the individual and combined effects of browning and loss of shading on the quantity (algal biomass) and nutritional quality (polyunsaturated fatty acid and sterol content) of the periphytic biofilm. We also conducted a field survey of differently colored (4.7 to 26.2 mg DOC L−1) streams to provide a ‘reality check’ for our experimental findings. Browning reduced greatly the algal biomass, suppressed the availability of essential polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA), and sterols, but increased the availability of terrestrial‐derived long‐chain saturated fatty acids (LSAFA). In contrast, loss of shading increased primary productivity, which resulted in elevated sterol and EPA contents of the biofilm. The field survey largely repeated the same pattern: biofilm nutritional quality decreased significantly with increasing DOC, as indicated particularly by a decrease of the ω‐3:ω‐6 ratio and increase in LSAFA content. Algal biomass, in contrast, was mainly controlled by dissolved inorganic nitrogen (DIN) concentration, while DOC concentration was of minor importance. The ongoing browning process is inducing a dramatic reduction in the nutritional quality of the stream biofilm. Such degradation of the major high‐quality food source available for stream consumers may reduce the trophic transfer efficiency in stream ecosystems, potentially extending across the stream‐forest ecotone.

Production, Processing, and Protection of Microalgal n-3 PUFA-Rich Oil.

Microalgae have been increasingly considered as a sustainable “biofactory” with huge potentials to fill up the current and future shortages of food and nutrition. They have become an economically and technologically viable solution to produce a great diversity of high-value bioactive compounds, including n-3 polyunsaturated fatty acids (PUFA). The n-3 PUFA, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), possess an array of biological activities and positively affect a number of diseases, including cardiovascular and neurodegenerative disorders. As such, the global market of n-3 PUFA has been increasing at a fast pace in the past two decades. Nowadays, the supply of n-3 PUFA is facing serious challenges as a result of global warming and maximal/over marine fisheries catches. Although increasing rapidly in recent years, aquaculture as an alternative source of n-3 PUFA appears insufficient to meet the fast increase in consumption and market demand. Therefore, the cultivation of microalgae stands out as a potential solution to meet the shortages of the n-3 PUFA market and provides unique fatty acids for the special groups of the population. This review focuses on the biosynthesis pathways and recombinant engineering approaches that can be used to enhance the production of n-3 PUFA, the impact of environmental conditions in heterotrophic cultivation on n-3 PUFA production, and the technologies that have been applied in the food industry to extract and purify oil in microalgae and protect n-3 PUFA from oxidation.

Higher Serum DHA and Slower Cognitive Decline in Patients with Alzheimer's Disease: Two-Year Follow-Up.

Omega-3 polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been associated with slower rates of cognitive decline. We investigated the association between omega-3 PUFAs and cognitive function in patients with Alzheimer’s disease (AD) receiving acetylcholinesterase inhibitors (AChEIs). This was a prospective cohort study using registered data. Patients with AD receiving AChEIs were recruited from 1 May 2016 to 30 April 2019 and were followed up for two years. Their daily diet record and blood concentration of omega-3 PUFAs were analyzed. Multiple linear and binary logistic regression was used to determine the factors associated with cognitive decline (continuous and dichotomized cognitive change). In the research, 129 patients with AD were identified with a mean age of 76.5 ± 6.6. Patients with AD with lower baseline omega-3 PUFAs levels were associated with a higher risk of cognitive decline than those with higher levels (odds ratio [OR] = 1.067, 95% confidence interval [CI]: 1.012, 1.125; p = 0.016) after adjustment. Patients with AD with a lower baseline DHA (OR = 1.131, 95% CI: 1.020, 1.254; p = 0.020), but not EPA, were associated with a higher risk of cognitive decline. We found that higher Mini-Nutritional Assessment scores (beta = −0.383, 95% CI = −0.182–−0.048, p = 0.001) and total fat (beta = −0.248, 95% CI = −0.067–−0.003, p = 0.031) were independently associated with slow cognitive decline in patients with AD receiving AChEIs. The baseline blood levels of omega-3 PUFAs were associated with cognitive decline in patients with AD receiving AChEIs. Future randomized controlled trials are needed to clarify whether this association is causal.

Association and Implications of Blood and Plaque n-3 Polyunsaturated Fatty Acid Composition in Patients Treated with Oral Eicosapentaenoic Acid before Carotid Endarterectomy.

Long-chain n-3 polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA), have been shown to prevent atherosclerosis-related cardiovascular disease, including stroke. Recently, the ratio of serum EPA to arachidonic acid (AA; EPA/AA ratio) has been reported to be a biomarker to prevent cardiovascular disease. In this study, we evaluate whether the serum EPA/AA ratio would be a useful biomarker for determining the efficacy of orally administered EPA in preventing stroke by investigating tissue and serum EPA/AA ratios, serum inflammatory markers, and carotid artery intimamedia thickness (IMT). Patients with dyslipidemia, as the primary illness scheduled for carotid endarterectomy (CEA), were included and randomly assigned to the EPA group (EPA: 1,800 mg/day plus statin; 10 patients) or non-EPA group (statin only; 15 patients). PUFA fraction was evaluated in the tissue (post-CEA) and serum (pre-CEA and 6 months thereafter). As for the tissue PUFA fraction in the plaque, the EPA group had a significantly higher EPA/AA ratio (EPA group, 0.46; non-EPA group, 0.28; p = 0.01). At 6 months postoperatively, the EPA group had a significantly higher serum EPA/AA ratio (baseline, 0.83; follow-up, 1.60; p = 0.05). No significant differences were found for inflammatory markers and IMT. Both serum and tissue EPA/AA ratios were higher in patients treated with oral EPA. Serum EPA/AA ratio might be a useful biomarker for the efficacy of orally administered EPA.

Eicosapentaenoic acid membrane incorporation stimulates ABCA1-mediated cholesterol efflux from human THP-1 macrophages

A high intake in polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) (C20:5 n-3), is cardioprotective. Dietary PUFAs incorporate into membrane phospholipids, which may modify the function of membrane proteins. We investigated the consequences of the membrane incorporation of several PUFAs on the key antiatherogenic ABCA1-mediated cholesterol efflux pathway. Human THP-1 macrophages were incubated with EPA, arachidonic acid (AA) (C20:4 n-6) or docosahexaenoic acid (DHA) (C22:6 n-3) for a long time to mimic a chronic exposure. EPA 70 μM, but not AA 50 μM or DHA 15 μM, increased ABCA1-mediated cholesterol efflux to apolipoprotein (apo) AI by 28% without altering aqueous diffusion. No variation in ABCA1 expression or localization was observed after EPA treatment. EPA incorporation did not affect the phenotype of THP-1 macrophages. The membrane phospholipids composition of EPA cells displayed higher levels of both EPA and its elongation product docosapentaenoic acid, which was associated with drastic lower levels of AA. Treatment by EPA increased the ATPase activity of the transporter, likely through a PKA-dependent mechanism. Eicosanoids were not involved in the stimulated ABCA1-mediated cholesterol efflux from EPA-enriched macrophages. In addition, EPA supplementation increased the apo AI binding capacity from macrophages by 38%. Moreover, the increased apo AI binding in EPA-enriched macrophages can be competed. In conclusion, EPA membrane incorporation increased ABCA1 functionality in cholesterol-normal human THP-1 macrophages, likely through a combination of different mechanisms. This beneficial in vitro effect may partly contribute to the cardioprotective effect of a diet enriched with EPA highlighted by several recent clinical trials.

Beneficial Outcomes of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on Human Health: An Update for 2021.

Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose–response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy.

The Role of Resolvins, Protectins and Marensins in Non-Alcoholic Fatty Liver Disease (NAFLD).

Increased triacylglycerols’ (TAG) synthesis, insulin resistance, and prolonged liver lipid storage might lead to the development of non-alcoholic fatty liver disease (NAFLD). Global prevalence of NAFLD has been estimated to be around 25%, with gradual elevation of this ratio along with the increased content of adipose tissue in a body. The initial stages of NAFLD may be reversible, but the exposition to pathological factors should be limited. As dietary factors greatly influence various disease development, scientists try to find dietary components, helping to alleviate the steatosis. These components include n-3 polyunsaturated (PUFA) fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA). This review focused on the role of resolvins, protectins and merensins in NAFLD.

Omega-3 PUFA profoundly affect neural, physiological, and behavioural competences - implications for systemic changes in trophic interactions.

In recent decades, much conceptual thinking in trophic ecology has been guided by theories of nutrient limitation and the flow of elements, such as carbon and nitrogen, within and among ecosystems. More recently, ecologists have also turned their attention to examining the value of specific dietary nutrients, in particular polyunsaturated fatty acids (PUFA), among which the omega-3 PUFA, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) play a central role as essential components of neuronal cell membranes in many organisms. This review focuses on a new neuro-ecological approach stemming from the biochemical (mechanistic) and physiological (functional) role of DHA in neuronal cell membranes, in particular in conjunction with G-protein coupled receptors (GPCRs). We link the co-evolution of these neurological functions to metabolic dependency on dietary omega-3 PUFA. We outline ways in which deficiencies in dietary DHA supply may affect, cognition, vision, and behaviour, and ultimately, the biological fitness of consumers. We then review emerging evidence that changes in access to dietary omega-3 PUFA may ultimately have profound impacts on trophic interactions leading to potential changes in community structure and ecosystem functioning that, in turn, may affect the supply of DHA within and across ecosystems, including the supply for human consumption.

N-3 fatty acid EPA supplementation in cancer patients receiving abdominal radiotherapy - A randomised controlled trial.

Malnutrition occurs frequently in patients with cancer during and after radiotherapy to the gastrointestinal (GI) and pelvic area and can lead to negative outcomes. N-3 fatty acids from fish, especially eicosapentaenoic acid (EPA) may possess anticachectic properties. The aim of this study was to investigate the effect of two nutritional interventions; dietary counselling and a daily oral nutritional supplement (ONS) containing 33.8g of protein and 2.2g EPA and 1.1g docosahexaenoic acid (DHA) or standard care, including dietary counselling and protein supplementation when needed. Outpatients commencing radiotherapy to the GI area were randomized to receive dietary counselling and daily supplementation over a 5-7-week period or standard care. Outcome parameters were measured at baseline (onset of radiotherapy), week 5, and 12 weeks after commencing radiotherapy, with one additional measurement of body weight at week 2. Quality of life (QoL) was measured using the EORTC QLQ-C30 questionnaire. Radiotherapy-related side effects were assessed using a questionnaire developed specifically for this study. Data from a historical control group collected in a previous observational study were included in this study to compare incidence of weight loss. In total, 30 patients were recruited to this study and 26 patients were enrolled and randomised. The rate of withdrawals was 7.7% at week 2, 15.4% at week 5, and 19.2% at week 12. In total, 22 patients completed the intervention. All the patients in the ONS-group and 85% in the control group experienced weight-loss. Using the intention to treat principle, there were no significant differences between groups in any of the outcomes. All patients experienced side effects. Five out of 11 patients consumed more than 75% of prescribed dose of the fish oil enriched oral nutritional supplement. Post hoc analysis showed that at week 2 the weight changed in high-compliant patients was+1.7% (1.0-2.6) compared with-0.7% (-2.8 to-0.1) in low compliant patients (p<0,01). The results indicated a dose-response relationship, as correlation analysis recovered a significant positive correlation between weight change and compliance to the fish oil enriched nutritional supplement at both week 2 and 5 (p<0.05 and p<0.01, respectively), but not at week 12, indicating a dose-response relationship during radiotherapy but not after. The proportion of patients experiencing weight loss throughout the study period was higher in this study (84.2%) than in the historical control group (73%) (p<0.05%). This study showed no effect from dietary counselling and intended protein/fish-oil supplementation on weight loss, quality of life, and nutritional intake, micronutrient status in plasma or radiotherapy-related side effects compared to the control group. However, the compliance to the fish oil enriched oral nutritional supplement was low. Post hoc analysis of dose-response relations indicate a positive correlation between the compliance and the ability to reduce weight loss in cancer patients during radiotherapy treatment. TRIAL REGISTRATION CLINICALTRIALS. NCT04687124.