地区性的动脉的僵硬上的 eicosapentaenoic 酸的效果: 由织物 Doppler 成像的评价

AIM:To evaluate the effects of eicosapentaenoic acid(EPA) on regional arterial stiffness assessed by strain rate using tissue Doppler imaging.METHODS:Nineteen eligible patients were prospectively studied(mean age 62 ± 8 years,68% men).Subjects with large vessel complications and/or diabetes mellitus were excluded.The strain rate of the ascending aorta was measured by tissue Doppler imaging as an index of regional arterial stiffness,and brachialankle pulse wave velocity(baPWV) was measured as an index of degree of systemic arteriosclerosis.These indices were compared before and after administration of EPA at 1800 mg/d for one year.RESULTS:The plasma concentration of EPA increased significantly after EPA administration(3.0% ± 1.1% to 8.5% ± 2.9%,P 【 0.001).There were no significant changes in baPWV(1765 ± 335 cm/s to 1745 ± 374 cm/s),low-density lipoprotein cholesterol levels(114 ± 29 mg/dL to 108 ± 28 mg/dL),or systolic blood pressure(131 ± 16 mmHg to 130 ± 13 mmHg) before and after EPA administration.In contrast,the strain rate was significantly increased by administration of EPA(19.2 ± 5.6 s-1,23.0 ± 6.6 s-1,P 【 0.05).CONCLUSION:One year of administration of EPA resulted in an improvement in regional arterial stiffness which was independent of blood pressure or serum cholesterol levels.

Fatty Acid Composition and Digestive Enzyme Activities of Rainbow Trout in Response to Dietary Docosahexaenoic Acid(DHA)and Eicosapentaenoic Acid(EPA)During Salinity Acclimation

This physiological study aimed to evaluate the effects of dietary docosahexaenoic acid(DHA)and eicosapentaenoic acid(EPA)on the fatty acid composition and digestive enzyme activities of rainbow trout(Oncorhynchus mykiss)during salinity acclimation.Rainbow trout with an average initial weight of 90.61 g±9.25 g were fed diets with the quantities of DHA and EPA equaling to 0.54%,0.95%,1.40%and 1.79%(abbreviated as DE-0.54,DE-0.95,DE-1.40,and DE-1.79,respectively)for eight weeks,after which the gastric and intestinal fatty acids composition were analyzed.Subsequently,the fish underwent salinity acclimation.On days 1,4,7,and 14 after the freshwater was replaced by seawater and at the end of the 8-week period,gastric and intestinal digestive enzyme activities were determined.The results showed that the gastric and intestinal DHA and EPA contents of the fish were positively correlated to their dietary DHA and EPA levels.Low dietary DHA and EPA levels inhibited the protease activity of rainbow trout.Fish in the DE-0.54 group increased the lipase activity to enhance the utilization of lipids maybe due to the inadequate essential fatty acids for fish in this group.Hence,rainbow trout in the DE-0.54 group failed to maintain suitable activities of digestive enzymes after salinity acclimation.Therefore,a diet with minimum 0.95%DHA and EPA levels is necessary for rainbow trout during salinity acclimation.

Research on Arachidonic Acid and Eicosapentaenoic Acid Anabolic Metabolism in Diasporangium sp.

The fatty acids of a strain of Diasporangium sp.had been analyzed by using GC-MS.The fatty acids of twenty mutants were determined.Based on these results,the producing of eicosapentaenoic acid(EPA)supposed via 18∶2,18∶3,20∶3,20∶4 which all belong to ω-6 fatty acids.The ω-3 desaturation was undertaken at arachidonic acid(AA).In addition,mutant strains resulted in enhanced content of AA which could get two times more than initial strain,but no compact on EPA.

Fatty Acid Treatment with Pure Omega-3 Eicosapentaenoic Acid Ethyl Ester for Patients with Cardiovascular Diseases: Differences between Branded (EPADEL®) and Generic Products

Background: Omega-3 polyunsaturated fatty acids (PUFAs) have some protective benefits for patients with coronary artery and cerebrovascular diseases. Eicosapentaenoic acid (EPA) drugs are prescribed as branded (B: EPADEL?) or generic products but no data exist concerning the differences in treatment outcomes between these products. Methods and Results: We investigated the differences in the serum levels of EPA, docosahexaenoic acid (DHA) and arachidonic acid (AA), and the EPA/AA ratios through blood sampling six months after daily administration of 1800 mg of EPADEL? and a generic EPA drug was initiated for 96 patients with cardiovascular diseases. All patients received these PUFA treatments while continuing with baseline therapy. After 6 months of administration, EPADEL? produced better results than the generic (G) product (EPA;baseline: 59.4 ± 25.5 μg, B: 215.5 ± 58.8 μg, G: 199.7 ± 63.8 μg, B vs G, p < 0.0005;AA;baseline: 197.4 ± 44.6 μg, B: 158.3 ± 36.3 μg, G: 163.6 ± 38.9 μg, B vs G, p < 0.02, as mean ± SD). Conclusions: There were clear differences between EPA branded and the generic products. Further study is required to determine whether the benefits from the branded product justify the higher price compared to the generic drug cost.

Solid Dose Form of Metformin with Ethyl Eicosapentaenoic Acid Does Not Improve Metformin Plasma Availability

Background: The purpose of the study was to investigate effects of ethyl eicosapentaenoic acid on pharmacokinetics of metformin. Pharmacokinetic profiles of metformin and ethyl eicosapentaenoic acid when delivered separately or together in solid dose form were investigated and compared to determine whether the solid dose resulted in an altered metforminpharmacokinetics when given with or without food. Methods: A single-center, open-label, repeated dose study investigated the pharmacokinetic (PK) profile of metformin when administered in solid dose form with ethyl eicosapentaenoic acid compared to co-administration with icosapent ethyl, an ester of eicosapentaenoic acid and ethyl alcohol used to treat severe hypertriglyceridemia with metformin hydrochloride. Non-compartmental PK methods were used to compare area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax) between patients randomized to either the ester or separate medications group under both fasting and fed conditions. Results: Using these two PK parameters, results showed that metformin availability was higher under fasting conditions when delivered separately from icosapent ethyl. There were no group differences in the fed condition. Conclusions: The solid dose form of metformin and ethyl eicosapentaenoic acid did not improve the pharmacokinetics of metformin in terms of plasma availability, suggesting that little is to be gained over the separate administration of ethyl eicosapentaenoic acid and metformin hydrochloride.

COMPARATIVE FATTY ACID COMPOSITION OF FOUR SARGASSUM SPECIES(FUCALES,PHAEOPHYTA)

Fatty acid composition of four Sargassum species from Qingdao and Shidao,Shandong Provincewas investigated.16:0（palmitic acid）was the major saturated fatty acid.C18 and C20were the mainpolyunsaturated fatty acids（PUFAs）.Arachidonic acid and eicosapentaenoic acid predominated amongpolyenoic acids in all the algal species examined.except for Sargassum sp.which had low concentrationof eicosapentaenoic acid.

Long-Term Effects of Docosahexaenoic Acid-Bound Phospholipids and the Combination of Docosahexaenoic Acid-Bound Triglyceride and Egg Yolk Phospholipid on Lipid Metabolism in Mice

The bioavailability of docosahexaenoic acid(DHA) and eicosapentaenoic acid(EPA) depends on their chemical forms. This study investigated the long-term effects of DHA-bound triglyceride(TG-DHA), DHA-bound phospholipid(PL-DHA), and the combination of TG-DHA and egg yolk phospholipid(Egg-PL) on lipid metabolism in mice fed with a high-fat diet(fat levels of 22.5%). Male C57BL/6J mice were fed with different formulations containing 0.5% DHA, including TG-DHA, PL-DHA, and the combination of TG-DHA and Egg-PL, for 6 weeks. Serum, hepatic, and cerebral lipid concentrations and the fatty acid compositions of the liver and brain were determined. The concentrations of serum total triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-c), and hepatic TG in the PL-DHA group and the combination group were significantly lower than those in the high-fat(HF) group(P < 0.05). Atherogenic index(AI) of the PL-DHA group was significantly lower than that of the combination group(P < 0.05). Hepatic TC level in the combination group was significantly lower than that in the HF group(P < 0.05), but no significant difference was observed between the combination group and the PL-DHA group. Both the PL-DHA and the combination groups showed significantly increased DHA levels in the liver compared with the HF group(P < 0.05). However, there were no obvious increases in the cerebral DHA levels in all DHA diet groups. These results suggest that PL-DHA was superior to the combination of TG-DHA and Egg-PL in decreasing the AI. Long-term dietary supplementation with low amount of DHA(0.5%) may improve hepatic DHA levels, although cerebral DHA levels may not be enhanced.

A defect in the activities of △~6 and △~5 desaturases and pro-resolution bioactive lipids in the pathobiology of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a low-grade systemic inflammatory condition, since liver and adipose tissue tumor necrosis factor-α (TNF-α) and TNF receptor 1 transcripts and serum TNF-α levels are increased and IL-6-/-mice are less prone to NAFLD. Fatty liver damage caused by high-fat diets is associated with the generation of pro-inflammatory prostaglandin E2 (PGE2). A decrease in the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the usefulness of EPA and DHA both in the prevention and management of NAFLD has been reported. AA, EPA and DHA and their anti-inflammatory products lipoxins (LXs), resolvins and protectins suppress IL-6 and TNF-α and PGE2 production. These results suggest that the activities of △6 and △5 desaturases are reduced in NAFLD and hence, the dietary essential fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) are not metabolized to their long-chain products AA, EPA and DHA, the precursors of anti-inflammatory molecules, LXs, resolvins and protectins that could prevent NAFLD. This suggests that an imbalance between proand anti-inflammatory bioactive lipids contribute to NAFLD. Hence, it is proposed that plasma and tissue levels of AA, EPA, DHA and LXs, resolvins and protectins could be used as predictors and prognostic biomarkers of NAFLD. It is suggested that the synthesis and use of more stable analogues of LXs, resolvins and protectins need to be explored in the prevention and management of NAFLD.

Dietary arachidonate in milk replacer triggers dual benefits of PGE2 signaling in LPS-challenged piglet alveolar macrophages

Background: Respiratory infections challenge the swine industry, despite common medicinal practices. The dual signaling nature of PGE2(supporting both inflammation and resolution) makes it a potent regulator of immune cell function. Therefore, the use of dietary long chain n-6 PUFA to enhance PGE2 effects merits investigation.Methods: Day-old pigs(n = 60) were allotted to one of three dietary groups for 21 d(n = 20/diet), and received either a control diet(CON, arachidonate = 0.5% of total fatty acids), an arachidonate(ARA)-enriched diet(LC n-6,ARA = 2.2%), or an eicosapentaenoic(EPA)-enriched diet(LC n-3, EPA = 3.0%). Alveolar macrophages and lung parenchymal tissue were collected for fatty acid analysis. Isolated alveolar macrophages were stimulated with LPS in situ for 24 h, and m RNA was isolated to assess markers associated with inflammation and eicosanoid production.Culture media were collected to assess PGE2 secretion. Oxidative burst in macrophages was measured by: 1)oxygen consumption and extracellular acidification(via Seahorse), 2) cytoplasmic oxidation and 3) nitric oxide production following 4, 18, and 24 h of LPS stimulation.Results: Concentration of ARA(% of fatty acids, w/w) in macrophages from pigs fed LC n-6 was 86% higher than CON and 18% lower in pigs fed LC n-3(P < 0.01). Following LPS stimulation, abundance of COX-2 and TNF-α mRNA(P < 0.0001), and PGE2 secretion(P < 0. 01) were higher in LC n-6 PAM vs. CON. However, ALOX5 abundance was1.6-fold lower than CON. Macrophages from CON and LC n-6 groups were 4-fold higher in ALOX12/15 abundance(P < 0.0001) compared to LC n-3. Oxygen consumption and extracellular acidification rates increased over 4 h following LPS stimulation(P < 0.05) regardless of treatment. Similarly, increases in cytoplasmic oxidation(P < 0.001)and nitric oxide production(P < 0.002) were observed after 18 h of LPS stimulation but were unaffected by diet.Conclusions: We infer that enriching diets with arachidonic acid may be an effective means to enhance a stronger innate immunologic response to respiratory challenges in neonatal pigs. However, further work is needed to examine long-term safety, clinical efficacy and economic viability.

The effects of EPA + DHA and aspirin on inflammatory cytokines and angiogenesis factors

Objective: In a recent study, we showed that the combination of aspirin plus the ω3 fatty acids eicosapen-taenoic acid (EPA) and docosahexaenoic acid (DHA) synergistically inhibited platelet function. As aspirin, EPA, and DHA have demonstrated anti-inflammatory properties, we hypothesized that the ingestion of EPA and DHA, with and without aspirin, would reduce plasma levels of inflammatory cytokines and angiogenesis factors more than aspirin alone and before aspirin was ingested. Methods: Using multiplex technology, we investigated the effects of aspirin (single-dose 650 mg on day 1), EPA + DHA (3.4 g/d for days 2 - 29), and aspirin with EPA + DHA (day 30) on plasma levels of inflammatory cytokines and angiogenesis factors in healthy adults. Results: Aspirin alone had no effect on any factor versus baseline, but EPA + DHA, with and without aspirin, significantly reduced concentrations of 8 of 9 factors. Although EPA + DHA plus aspirin reduced concentrations of a subset of the factors compared to baseline, neither aspirin alone nor the combination significantly reduced the level of any analyte more robustly than EPA + DHA alone. Conclusions: These data suggest that EPA + DHA has more pronounced down-regulatory effects on inflammation and angiogenesis than aspirin. The implications of these findings for the use of combined therapy for cardiovascular disease remain to be clarified.

Polyunsaturated fatty acids and DNA methylation in colorectal cancer

Colorectal cancer(CRC) has been designated a major global problem, especially due to its high prevalence in developed countries. CRC mostly occurs sporadically(75%-80%), and only 20%-25% of patients have a family history.Several processes are involved in the development of CRC such as a combination of genetic and epigenetic alterations. Epigenetic changes, including DNA methylation play a vital role in the progression of CRC. Complex interactions between susceptibility genes and environmental factors, such as a diet and sedentary lifestyle, lead to the development of CRC. Clinical and experimental studies have confirmed the beneficial effects of dietary polyunsaturated fatty acids(PUFAs) in preventing CRC. From a mechanistic viewpoint, it has been suggested that PUFAs are pleiotropic agents that alter chromatin remodeling,membrane structure and downstream cell signaling. Moreover, PUFAs can alter the epigenome via modulation of DNA methylation. In this review, we summarize recent investigations linking PUFAs and DNA methylationassociated CRC risk.

Fatty Acids and Autism Spectrum Disorders: The Rett Syndrome Conundrum

Autism spectrum disorders (ASDs) are epidemically explosive clinical entities, but their pathogenesis is still unclear and a definitive cure does not yet exist. Rett syndrome (RTT) is a rare genetically determined cause of autism linked to mutations in the X-linked MeCP2 gene or, more rarely, in CDKL5 or FOXG1. A wide phenotypical heterogeneity is a known feature of the disease. Although several studies have focused on the molecular genetics and possible protein changes at different levels, to date very little attention has been paid to fatty acids in this disease, which could be considered as a natural paradigm for the ASDs. To this regard, a quite enigmatic feature of the disease is the evidence in the affected patients of an extensive peroxidation of polyunsaturated fatty acids (arachidonic acid, AA, docosaexahenoic acid, DHA, adrenic acid, AdA and, to a lesser extent, eicosapentaenoic acid, EPA), in contrast with amelioration of the redox changes and phenotypical severity following the supplementation of some of those same fatty acids (DHA + EPA). Therefore, fatty acids may represent a kind of Janus Bifrons in the particular context of RTT. Here, we propose a rational explanation for this apparent “fatty acid paradox” in RTT. A better understanding of this paradox could also be of help to get a better insight into the complex mechanism of action for polyunsaturated fatty acids in health and disease.

Correlation of Various Foods Intakes and Plasma Levels of Omega Fatty Acids in Healthy Japanese Old Men

Background: Trans fatty acids are considered to impair health and some ω fatty acids are protective against atherosclerosis and diabetes mellitus. Trans fatty acids are said to be formed by the partial hydrogenation of vegetable oils. Some amounts are produced in digestive organs of ruminants and present in dairy products or meat. It is important how much these intaken fatty acids influence their plasma levels. Methods: Plasma levels of fatty acids including transforms of healthy old men are measured by gas chromatography and correlations between various foods intakes and plasma levels of trans fatty acids, and ω fatty acids are examined. Results: Intake of fish resulted in increase in plasma levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) but intake of meat such as beef, cow and chicken meat did not increase plasma levels of arachidonic acid (AA). Intakes of oils increased plasma levels of dihomo-g-linolenic acid significantly and AA to some extent. Conclusion: Plasma levels of EPA and DHA increased upon intakes of fish in Japanese old men. Oil intake but not meat intake increased DGLA significantly. These results may explain low incidence of cardiovascular diseases in Japanese people compared with American people whose plasma levels of DHA and EPA are lower.

Dietary and Nutritional Value of Fish Oil,and Fermented Products

Present review article explains the dietary and nutritional value of various fish derived natural food products.Fish is a good source of important nutrients such as proteins,fats,vitamins and minerals.Fish oil contains polyunsaturated fatty acids(PUFAs)mainly omega-3 fatty acids,eicosapentaenoic acid(EPA),docosahexaenoic acid(DHA),and eicosanoids.Fish contains high-quality protein(~14-16 percent)and is consumed worldwide.This article also emphasizes therapeutic uses of fish nutrients and oil in healing of wounds,hyper pigmentation,dermatitis,and in cardiovascular risks.Fish oil polyunsaturated fatty acids(PUFAs)are highly beneficial in cardiovascular problems and dermatitis.Fish oil is good for skin-related diseases such as photo-ageing and melanogenesis These also affect anticancer,wound healing and anti-depressant activity.In the present review various local,national,and international processed fish derived food currently available in the market fish dishes have been mentioned.

Correlation between bioactive lipids and novel coronavirus:constructive role of biolipids in curbing infectivity by enveloped viruses,centralizing on EPA and DHA

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)belongs to the family coronaviridae.It is spherical and possesses proteins called spikes,which can clamp onto the human cells.Once in close interaction with the human cells,these viruses undergo structural change and can fuse with the cell membrane.The virus enters the host and starts the process of translation and transcription in the cells and uncoated genome,respectively.Due to the rapid transmittable nature of the virus,extant actions should be taken.The fatty acids administrated orally,or intravenously,could help us gear things up in providing resistance and preventing infection.Hence,the multiplication of the virus could be hindered by arachidonic acid,eicosapentaenoic acid(EPA),and docosahexaenoic acid(DHA).In that context,the current review highlights the role of these unsaturated fatty acids and their derivatives such as lipoxins and resolvins in the inactivation of the enveloped coro-navirus disease 2019(COVID-19).

Effects of N-3 Fatty Acids on the Coronary Heart Disease Patients

Objectives To evaluate the effects of n-3 fatty acids on the coronary heart disease patients. Methods From September 2007 to March 2008, 60 patients with coronary heart disease were randomly assigned to n-3 fatty acids group (group N) and control group (group C). Both groups received standard coronary artery disease secondary prevention treatment and group N also received eicosapentaenoic acid (EPA) 1.8 g plus docosahexaenoic acid (DHA) 1.2 g per day for 12 weeks. Plasma triacylglycerols, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and blood pressure were measured before and after the study. Results Plasma triacylglycerols, blood pressure and LDL-C level were lower in group N after n-3 fatty acids treatment while no change was found in group C (P<0.05). HDL-C level slightly increased and total cholesterol level slightly decreased after n-3 fatty acids but both change were not significant (P>0.05). Conclusions N-3 fatty acids have beneficial effects on the coronary artery disease patients.