Eicosapentaenoic acid代谢产物促进胰岛α细胞转分化为胰岛β细胞的作用研究

目的 探讨eicosapentaenoic acid(EPA)代谢产物促进胰岛α细胞向β细胞转分化的作用。方法 雄性C57BL/6J小鼠连续5 d腹腔注射60 mg/kg链脲佐霉素(streptozocin, STZ)构建1型糖尿病(T1DM)小鼠模型,2周后随机分为模型组、97%EPA饮食干预组、75%鱼油(50%EPA+25%DHA)饮食干预组,每周检测随机血糖;模型到期后,通过免疫荧光染色观察小鼠胰腺中胰岛β细胞再生情况。提取tdTomato荧光蛋白特意标记α细胞的小鼠(GCGicre小鼠与Rosa26tdTomato小鼠杂交获得)胰岛,加入1 mmol·L^(-1)STZ诱导β细胞凋亡,添加EPA代谢产物,培养48 h后,利用荧光染色观察胰岛素和tdTomato荧光的表达。在小鼠胰岛α细胞系αTC1培养基中添加EPA代谢产物,48 h后,利用荧光染色观察胰岛素和胰高血糖素的表达。结果 EPA和鱼油饮食干预均可明显降低T1DM小鼠的血糖水平,改善葡萄糖稳态,且胰腺中出现胰岛素和胰高血糖素共定位细胞;EPA代谢产物引起已发生β细胞凋亡的小鼠胰岛中发生tdTomato荧光蛋白和胰岛素共定位;EPA代谢产物可促进胰岛αTC1细胞系细胞分泌胰岛素。结论 EPA及其代谢产物可通过促进胰岛α细胞转分化为β细胞,进而增加胰岛素的分泌,缓解T1DM小鼠的高血糖症状。

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.

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.

Effects of Nutritional Factors on the Growth and Heterotrophic Eicosapentaenoic Acid Production of Diatom Nitzschia laevis

The effects of several nutritional factors on the growth and eicosapentaenoic acid （EPA） production of diatom Nitzschia laevis were studied. 4LDM （quadrupled concentration of the nutrient salt） was the optimal concentration of nutrient salt for the growth and EPA production ofN. laevis. The growth ofN. laevis was inhibited when the glucose concentration was either lower than 10gL^-1 or higher than 15 gL^-1. Both sodium nitrate and urea were good nitrogen sources for the growth and EPA production, while ammonium chloride seriously decreased the dry cell weight （DW） and the EPA content. Silicate seriously influenced the growth of N. laevis. The maximum DW of 2.34 gL^-1 was obtained in the presence of 150 mgL^-1 Na2SiO3· 9H2O. The EPA content remained almost the same when the silicate concentration was lower than 150mgL^-1; however, higher silicate concentrations resulted in a steady decrease of EPA content. Low medium salinity （≤29） did not seem to influence the DW of N. laevis, and high salinity resulted in a decrease of DW. The highest EPA content （4.08%） and yield （110mgL^-1） were observed at the salinity of 36 and 29, respectively. Key words polyunsaturated fatty acid; eicosapentaenoic acid; microalga; Nitzschia laevis; heterotrophy

Effects of Temperature, Salinity, Light Intensity, and pH on the Eicosapentaenoic Acid Production of Pinguiococcus pyrenoidosus

The effects of temperature, light intensity, salinity, and initial pH on the growth and fatty acid composition of Pinguiococcus pyrenoidosus 2078 were studied for eicosapentaenoic acid (EPA) production potential. The fatty acid composition was assayed by gas chromatography-mass spectrometry, which indicated that the main fatty acids were C14:0, C16:0 and EPA. The highest EPA percentage 20.83% of total fatty acids was obtained at 20℃ with the temperature being set at 20, 24, and 28℃. Under different salinities and light intensities, the highest percentages of total polyunsaturated fatty acids (PUFAs) and EPA were 17.82% and 31.37% of total fatty acids, respectively, which were achieved at salinity 30 and 100μmol photon m-2s-1 illumination. The highest percentages of total PUFAs and EPA were 38.75% and 23.13% of total fatty acids, respectively, which were reached at an initial pH of 6 with the test range being from 5.0 to 9.0.

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.

Effect of eicosapentaenoic acid on regional arterial stiffness:Assessment by tissue Doppler imaging

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 brachial-ankle 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.

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.

Preparation of DHA-and EPA-enriched Glycerides by Enzymatic Interesterification Using Tuna Oil and Capric Acid

This study focused on the preparation of docosahexaenoic acid(DHA) and eicosapentaenoic acid(EPA)enriched-triacylglycerols by enzymatic interesterification using tuna oil and capric acid. The content of DHA+EPA is 26.86% in the tuna oil used in this study. A response surface methodology(RSM) was used to optimize the reaction parameters(reaction temperature, substrate molar ratio, enzyme amount and reaction time), and the optimized conditions were determined to be: reaction temperature 58℃, substrate molar ratio(capric acid : tuna oil) 4:1, enzyme amount 4%, and reaction time 7.5 h. Under the optimized conditions, the content of DHA+EPA in the glycerides was 40.03%, which is 13.17% higher than that in raw tuna oil. In addition,the MLM-type structured lipids containing medium chain fatty acids(capric acid) at positions sn-1,3 and a long chain fatty acid(DHA/EPA) at the position sn-2 may have many health benefits for humans.

Optimization of High EPA Structured Phospholipids Synthesis from （u-3 Fatty Acid Enriched Oil and Soy Lecithin

The molecular structure of phospholipids can be changed enzymatically to obtain different tailor-made phospholipids. Incorporation of ω-3 fatty acids into phospholipids structure increased their oxidative stability, suggesting more health beneficial phospholipids. This study aimed to optimize eicosapentaenoic acid （EPA） incorporation into phospholipids structure by acidolysis reaction using free lipase （EC 3.1.1.3） from Rhizomucor miehei. Deoiled soy lecithin from anjasmoro variety was used as phospholipids source, while ω-3 fatty acid enriched oil was used as acyl source. Oil enriched with ω-3 fatty acids was obtained from low temperature solvent crystallization of lemuru （Sardinella longiceps） by-product. Response surface methodology （RSM） was used in this study to determine the relationship between the three factors （enzyme concentration, reaction time and substrate ratio） and their effects on EPA incorporation into soy lecithin structure. The results showed that the relation between EPA content with three factors （reaction time, enzyme concentration and substrate ratio） was quadratic. The significant factors were substrate ratio and reaction time. Optimum conditions at a ratio of 3.77：1 between ω-3 fatty acids enriched oil and soy lecithin, 30% lipase concentration, and 24.08 h reaction time, gave 22.81% of EPA content of structured phospholipids.

Diet switch and omega-3 hydroxy-fatty acids display differential hepatoprotective effects in an obesity/nonalcoholic fatty liver disease model in mice

AIM To study the effect of 18-hydroxy-eicosapentaenoic acid(18-HEPE) and 17-hydroxy-docosahexaenoic acid(17-HDHA) in a murine model of obesity/nonalcoholic fatty liver disease.METHODS C57 BL/6 mice were fed with standard chow diet(CD) or high-fat, fructose-enriched diet(HFD) for 16 wk. Then, three groups were treated for 14 d with either, diet switch(HFD for CD), 18-HEPE, or 17-HDHA. Weightand fasting glucose were recorded on a weekly basis. Insulin tolerance test was performed at the end of treatment. Histological analysis(HE and Masson's trichrome stain) and determination of serum insulin, glucagon, glucagon-like peptide 1(GLP-1), glucose-dependent insulinotropic polypeptide, adiponectin and resistin were carried out as well as liver proteins by western blot.RESULTS Mice treated with hydroxy-fatty acids 18-HEPE and 17-HDHA displayed no weight loss or improved insulin sensitivity. However, these mice groups showed a significant amelioration on serum GLP-1, adiponectin and resistin levels. Also, a significant reduction on inflammatory infiltrate was observed at both portal and lobular zones. Furthermore, up-regulation of PPARα/γ protein levels was observed in liver tissue and it was associated with decreased levels of NF-κB also determined by western blot analysis. On the other hand, diet switch regimen resulted in a marked improvement in most parameters including: weight loss, increased insulin sensitivity, decreased steatosis, restored levels of insulin, glucagon, leptin, adiponectin and resistin. However, no significant changes were observed regarding inflammatory infiltrate in this last group.CONCLUSION 18-HEPE and 17-HDHA differentially exert hepatoprotective effects through up-regulation of nuclear receptors PPARα/γ and amelioration of serum adipokines profile.

轮枝霉(Diasporangiumsp.)产生EPA、AA发酵条件的初步研究

对本实验室分离的轮枝霉 (Diasporangiumsp )发酵产生含EPA、AA等多不饱和脂肪酸的条件 ,如碳源种类、氮源种类、pH、菌种的接种量和种龄、培养温度、通气量进行了研究 ,摇瓶发酵结果表明 ,以玉米粉和葡萄糖混合作为碳源能获得最高的不饱和脂肪酸产量 ;有机氮源有利于菌丝不饱和脂肪酸的产生 ;低温有利于菌丝中长链不饱和脂肪酸的产生 ,发酵接种量宜大 ;pH对菌丝生物量、EPA和AA的含量均有显著的影响。发酵培养 6d后菌丝中的不饱和脂肪酸含量达到最大值。在初步优化培养条件下 ,EPA、AA分别达到 2 5 3 7mg/L和 5 49 8mg/L。

提取及培养条件对紫球藻AA与EPA的影响

研究了紫球藻脂肪酸提取过程中不同的预处理方法(碾磨处理、超声波处理及未预处理)及提取分析方法(KOH-甲醇法、乙醚-石油醚法、氯仿-甲醇法、乙醇法、HCl-甲醇法)对紫球藻二十碳四烯酸与二十碳五烯酸的影响,结果表明,碾磨预处理是紫球藻不饱和脂肪酸二十碳四烯酸(AA)及二十碳五烯酸(EPA)检测效果最好且简便经济的方法,而氯仿-甲醇法对紫球藻AA及EPA的气相色谱(GC)分析效果最优,在同等条件下其灵敏度高,所取得的长链不饱和脂肪酸甲酯的产物多,EPA达到1.159mg/g,AA达到2.062mg/g;其他方法依次按效果排序为:乙醚-石油醚法>乙醇法>KOH-甲醇法>HCl-甲醇法。同时研究了不同培养时间对紫球藻AA与EPA组成的影响,结果表明,对数前期第6d为收获EPA的最佳时间,含量达到10.671mg/g;对数期末第8d为收获AA的最佳时期,含量达到19.415mg/g。

气相色谱法测定鱼油微胶囊中EPA和DHA的含量

鱼油富含ω-3不饱和脂肪酸,主要包括二十碳五烯酸(Eicosapentaenoic acid,EPA)和二十二碳六烯酸(Docosahexaenoic acid,DHA)。本文主要研究了用气相色谱内标法测定鱼油微胶囊产品中的EPA和DHA的含量。在充氮保护下,采用氢氧化钾-甲醇酯化法将鱼油微胶囊中的脂肪酸快速、有效地转化成脂肪酸甲酯,以二十一碳脂肪酸甲酯为内标,建立了EPA和DHA的定量分析法。使用HP-INNVOWAX毛细管柱(30m×0.25mm×0.25μm),载气为氦气,其流速为1.8mL/min,检测器温度为280℃。该方法对EPA和DHA定量分析的相对标准偏差分别为1.09%和1.05%,平均回收率分别为99.5%和99.3%。此检测方法简便快速、准确度高,适合于对大量样品的分析。

影响腐霉发酵培养中菌丝形态的因素及其与EPA含量的关系

研究了发酵培养中影响腐霉菌丝形态的因素及其与EPA(二十碳五烯酸)含量的关系.结果表明,接种量、起始pH值、温度、添加物对腐霉菌丝形态影响较大,接种量3%～10%,培养温度25～30℃,起始pH4及pH6.5～9,添加植物油能使菌丝保持直径小于5mm的分散小球状态.同时,起始pH值及培养温度显著影响EPA含量.较低pH值和低温培养均有利于菌丝内EPA积累.

超临界CO_2从扁藻中萃取EPA和DHA的研究

研究采用超临界 CO2 从扁藻中萃取 EPA和 DHA的最优化工艺条件 ( A2 B2 C3D3) ,得最高萃取率 EPA为91 .3 % ,DHA为 87.4 % ,该法比溶剂法优越 ,为开发和综合利用海藻资源开辟了新的应用途径。

脂肪酶富集DHA和EPA的研究进展

综述了脂肪酶在富集DHA和EPA方面的应用 ,总结了近十年来脂肪酶富集DHA和EPA的研究状况 。

超临界CO_2从南海翡翠贻贝中萃取EPA和DHA的研究

用超临界ＣＯ２对南海翡翠贻贝中萃取二十碳五烯酸（ＥＰＡ）和二十二碳六烯酸（ＤＨＡ）工艺进行了研究，得出其最佳工艺条件为：压力３５ＭＰａ，温度３５℃，ＣＯ２用量２ｍｌ／ｇ料，尿素用量为乙酯量的１０％。乙酯的萃取率达到６１．５％。ＥＰＡ和ＤＨＡ乙酯总含量（ｗ）达到２８３２％。

尿素包合法富集鱼油中的EPA和DHA的研究

用尿素包合法（脲包法）对大连鱼油中的ＥＰＡ和ＤＨＡ进行富集，得到较佳操作条件为温度０℃，脲酯比１３，鱼油甲酯为脲包客体，以甲醇作溶剂。