Docosahexaenoic acid ethyl ester

Geometrical and positional isomers of unsaturated furan fatty acids in food.[Pubmed:36408796]

Lipids. 2023 Mar;58(2):69-79.

Furan fatty acids (FuFA) are important antioxidants found in low concentrations in many types of food. In addition to conventional FuFA which normally feature saturated carboxyalkyl and alkyl chains, a few previous studies indicated the FuFA co-occurrence of low shares of unsaturated furan fatty acids (uFuFA). For their detailed analysis, the potential uFuFA were enriched by centrifugal partition chromatography (CPC) or countercurrent chromatography (CCC) followed by silver ion chromatography from a 4,7,10,13,16,19-Docosahexaenoic acid ethyl ester oil, a 5,8,11,14,17-eicosapentaenoic acid ethyl ester oil and a latex glove extract. Subsequent gas chromatography with mass spectrometry (GC/MS) analysis enabled the detection of 16 individual uFuFA isomers with a double bond in conjugation with the central furan moiety. In either case, four instead of two uFuFA isomers previously reported in food, respectively, were detected by GC/MS. These isomers showed characteristic elution and abundance patterns in GC/MS chromatograms which indicated the presence of two pairs of cis/trans-isomers (geometrical isomers).

Early detection of lipid oxidation in infant milk formula by measuring free oxylipins-Comparison with hydroperoxide value and thiobarbituric acid reactive substance methods.[Pubmed:36398751]

J Food Sci. 2022 Dec;87(12):5252-5262.

Infant milk formula was used as a model food to compare the sensitivity of thiobarbituric acid reactive substances (TBARS) and hydroperoxide methods to UPLC-MS/MS oxylipin analysis for detecting early lipid oxidation. Two different infant milk formulas were tested during 21 days of storage at 4 degrees C. Formulas 1 and 2 contained canola oil and canola oil + 1% Docosahexaenoic acid ethyl ester, respectively. Formulas were sampled up to 21 days of storage. Formula 2 had higher peroxide values than Formula 1 across all time points. However, no significant differences over time in TBARS and peroxide values in either formula were observed. Several oxylipins increased in both formulas starting on day 7 (linoleic acid and alpha-linolenic acid-derived oxylipins in Formula 1 and DHA-derived oxylipins in Formula 2). These results indicate that free oxylipins are effective in detecting early lipid oxidation and distinguishing between formulations containing different fatty acids. PRACTICAL APPLICATION: We have recently shown that primary oxidation products known as oxylipins can be measured in their free form by ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to detect early lipid oxidation. However, a head-to-head comparison of the sensitivity of this approach to conventional spectrophotometric methods has not been evaluated. Our results indicate that free oxylipin measurements are better than conventional methods in detecting early lipid oxidation in milk infant formula distinguishing between different formulations.

Multi-omics analysis reveals the host-microbe interactions in aged rhesus macaques.[Pubmed:36238598]

Front Microbiol. 2022 Sep 27;13:993879.

Aging is a complex multifactorial process that greatly affects animal health. Multi-omics analysis is widely applied in evolutionary biology and biomedical research. However, whether multi-omics can provide sufficient information to reveal comprehensive changes in aged non-human primates remains unclear. Here, we explored changes in host-microbe interactions with aging in Chinese rhesus macaques (Macaca mulatta lasiota, CRs) using multi-omics analysis. Results showed marked changes in the oral and gut microbiomes between young and aged CRs, including significantly reduced probiotic abundance and increased pathogenic bacterial abundance in aged CRs. Notably, the abundance of Lactobacillus, which can metabolize tryptophan to produce aryl hydrocarbon receptor (AhR) ligands, was decreased in aged CRs. Consistently, metabolomics detected a decrease in the plasma levels of AhR ligands. In addition, free fatty acid, acyl carnitine, heparin, 2-(4-hydroxyphenyl) propionic acid, and Docosahexaenoic acid ethyl ester levels were increased in aged CRs, which may contribute to abnormal fatty acid metabolism and cardiovascular disease. Transcriptome analysis identified changes in the expression of genes associated with tryptophan metabolism and inflammation. In conclusion, many potential links among different omics were found, suggesting that aged CRs face multiple metabolic problems, immunological disorders, and oral and gut diseases. We determined that tryptophan metabolism is critical for the physiological health of aged CRs. Our findings demonstrate the value of multi-omics analyses in revealing host-microbe interactions in non-human primates and suggest that similar approaches could be applied in evolutionary and ecological research of other species.

Development of certified reference materials for four polyunsaturated fatty acid esters.[Pubmed:35561511]

Food Chem. 2022 Sep 30;389:133006.

Certified reference materials (CRMs) with high accuracy and traceability are essential tools for the validation of analytical methods and calibration of equipment. In this study, purity CRMs for four polyunsaturated fatty acids (PUFAs) esters, namely, cis-(4,7,10,13,16,19)- Docosahexaenoic acid methyl ester (DHA-ME), cis-4,7,10,13,16,19- Docosahexaenoic acid ethyl ester (DHA-EE), cis-(5,8,11,14,17)- Eicosapentaenoic acid methyl ester (EPA-ME) and cis-(5,8,11,14,17)- Eicosapentaenoic acid ethyl ester (EPA-EE), were first developed according to the ISO Guide. The CRMs' purity values were assigned based on the average of quantitative nuclear magnetic resonance and mass balance approaches. The certified value with expanded uncertainties (k = 2, 95% confidence interval) were determined to be (98.8 +/- 0.4) %, (99.0 +/- 0.3) %, (98.9 +/- 0.4) % and (98.9 +/- 0.4) % for DHA-ME, DHA-EE, EPA-ME and EPA-EE, respectively. The four PUFAs esters were homogeneous and stable for 12 months at -4 degrees C and 7 days at 50 degrees C.

Vascepa protects against high-fat diet-induced glucose intolerance, insulin resistance, and impaired beta-cell function.[Pubmed:34458694]

iScience. 2021 Jul 28;24(8):102909.

Omega-3 fatty acid prescription drugs, Vascepa (>/=96% eicosapentaenoic acid [EPA] ethyl ester) and Lovaza (46.5% EPA and 37.5% Docosahexaenoic acid ethyl ester) are known therapeutic regimens to treat hypertriglyceridemia. However, their impact on glucose homeostasis, progression to type 2 diabetes, and pancreatic beta cell function are not well understood. In the present study, mice were treated with Vascepa or Lovaza for one week prior to six weeks of high-fat diet feeding. Vascepa but not Lovaza led to reduced insulin resistance, reduced fasting insulin and glucose, and improved glucose intolerance. Vascepa improved beta cell function, reduced liver triglycerides with enhanced expression of hepatic fatty acid oxidation genes, and altered microbiota composition. Vascepa has protective effects on diet-induced insulin resistance and glucose intolerance in mice.

Alterations in the Fecal Microbiome and Metabolome of Horses with Antimicrobial-Associated Diarrhea Compared to Antibiotic-Treated and Non-Treated Healthy Case Controls.[Pubmed:34204371]

Animals (Basel). 2021 Jun 17;11(6):1807.

Diarrhea is an adverse effect of antimicrobial therapy in horses. This matched, case-controlled study compared the fecal microbiome and metabolome of horses on antibiotics that developed diarrhea (AAD, n = 17) to those that did not develop diarrhea (ABX, n = 15) and to a control population not exposed to antibiotics (CON, n = 31). Fecal samples were collected from horses that were matched for diet and antimicrobial agent (including dose, route, and duration of therapy). Illumina sequencing of 16S rRNA genes was performed, and QIIME 2.0 was used to generate alpha and beta diversity metrics. Untargeted metabolomics using GC-MS platforms was performed and analyzed using Metaboanalyst 5.0. Microbiome composition was significantly different in AAD compared to CON (ANOSIM, R = 0.568, p = 0.001) but not to ABX (ANOSIM, R = 0.121, p = 0.0012). AAD and ABX horses had significantly decreased richness and evenness compared to CON horses (p < 0.05). Horses on antimicrobials (AAD and ABX) had significant changes in 14 phyla compared to CON horses. Only Verrucomicrobia distinguished AAD from ABX and CON horses (q = 0.0005). Metabolite profiles of horses with AAD clustered separately from ABX and CON horses. Seven metabolites were found to be significantly different between groups (p < 0.05): L-tyrosine, kynurenic acid, xanthurenic acid, 5-hydroxyindole-3-acetic acid, Docosahexaenoic acid ethyl ester, daidzein, and N-acetyltyramine. Metabolite profiles of horses on antimicrobials, especially those with AAD, are altered compared to CON horses.

A biphasic system based on guanidinium ionic liquid: Preparative separation of eicosapentaenoic acid ethyl ester and docosahexaenoic acid ethyl ester by countercurrent chromatography.[Pubmed:31959458]

J Chromatogr A. 2020 May 10;1618:460872.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are high nutritional components. Evidence for unique effects of them is increasing. Further understanding of their independent biological functions urgently needs more efficient separation techniques. Nowadays, most of the commercially available fish oil products are the mixture of eicosapentaenoic acid ethyl ester (EPAEE) and Docosahexaenoic acid ethyl ester (DHAEE). It will be convenient to directly separate esterified EPA and DHA without saponification pretreatment. However, it is of great challenge to separate EPAEE and DHAEE because of their extremely fat-soluble nature and the equivalent chain length rule. In this research, the suitability of green guanidinium ionic liquid (IL) in countercurrent chromatography (CCC) solvent system for the separation of them was evaluated for the first time. Compared with imidazolium IL and phosphonium IL, guanidinium IL based non-aqueous biphasic system showed more outstanding separation performance. The separation mechanism was elucidated in depth through quantum mechanical calculations. It was found that guanidinium IL acted a crucial role in the CCC separation, which resulted in difference of partition behavior of EPAEE and DHAEE via different hydrogen-bonding affinity. EPAEE and DHAEE were successfully separated by solvent system (n-heptane/methanol/propylguanidinium chloride ([C(3)Gun]Cl, 1:1:5%, v/v/m)) with high purity (>95%) in one step, which was not achieved beforehand. Moreover, an easy recycling procedure of IL had also been devised, which significantly reduced waste generated. It opens up a new way for reasonable design water-free two-phase solvent system for efficient separation of very non-polar lipid compounds.

[Separation of eicosapentaenoic acid ethyl ester and docosahexaenoic acid ethyl ester by simulated moving bed chromatography].[Pubmed:30251513]

Se Pu. 2018 Sep 8;36(9):858-865.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are important omega -3 polyunsaturated fatty acids. Their physiological effects on humans are not exactly the same; therefore, the production of products with high-purity EPA or DHA monomers is significant. In this work, EPA ethyl ester (EPA-EE) and DHA ethyl ester (DHA-EE) were first separated using HPLC with poly(styrene-co-divinylbenzene) (PS/DVB) as the stationary phase. The effects of the mobile phase, PS/DVB particle diameter, and column temperature were systematically evaluated. The results showed that methanol is a suitable mobile phase, having a resolution of 2.75. By comparing resolutions, a PS/DVB particle diameter of 10 mu m was chosen; however, when the pressure drop of PS/DVB is considered, PS/DVB with a particle diameter of 20 mu m is more favorable for large-scale preparations. A column temperature of 40℃ was found to be the most feasible for maintaining efficient separation. Second, eight semi-preparative columns (150 mmx10 mm) of PS/DVB polymer were prepared for the simulated moving bed (SMB) chromatography; the homogeneity of these columns was perfect, with a relative total column porosity error of less than 1%. Finally, an EPA-EE and DHA-EE mixture was separated using the SMB chromatography, and the contents of the extract and the raffinate were determined using GC-FID. The effects of the flow rate of Zone Ⅱ and Zone Ⅲ, the flow rate of the feed, and the feed concentration were investigated. Under optimal conditions, EPA-EE and DHA-EE with favorable purities of 91.6% and 93.6%, respectively, were achievable. The recovery of the EPA-EE was 97.0% and the recovery of the DHA-EE was 91.6%. The productivity and solvent requirements were 5.97 g/(L\5h) and 1.52 L/g, respectively. Therefore, SMB chromatography is an attractive technology for the production of high-value products.

The hydroxylated form of docosahexaenoic acid (DHA-H) modifies the brain lipid composition in a model of Alzheimer's disease, improving behavioral motor function and survival.[Pubmed:28284721]

Biochim Biophys Acta Biomembr. 2017 Sep;1859(9 Pt B):1596-1603.

We have compared the effect of the commonly used omega-3 fatty acid, Docosahexaenoic acid ethyl ester (DHA-EE), and of its 2-hydroxylated DHA form (DHA-H), on brain lipid composition, behavior and lifespan in a new human transgenic Drosophila melanogaster model of Alzheimer's disease (AD). The transgenic flies expressed human Abeta42 and tau, and the overexpression of these human transgenes in the CNS of these flies produced progressive defects in motor function (antigeotaxic behavior) while reducing the animal's lifespan. Here, we demonstrate that both DHA-EE and DHA-H increase the longer chain fatty acids (>/=18C) species in the heads of the flies, although only DHA-H produced an unknown chromatographic peak that corresponded to a non-hydroxylated lipid. In addition, only treatment with DHA-H prevented the abnormal climbing behavior and enhanced the lifespan of these transgenic flies. These benefits of DHA-H were confirmed in the well characterized transgenic PS1/APP mouse model of familial AD (5xFAD mice), mice that develop defects in spatial learning and in memory, as well as behavioral deficits. Hence, it appears that the modulation of brain lipid composition by DHA-H could have remedial effects on AD associated neurodegeneration. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escriba.

Kinetics of docosahexaenoic acid ethyl ester accumulation in dog plasma and brain.[Pubmed:27720035]

Prostaglandins Leukot Essent Fatty Acids. 2016 Oct;113:1-8.

This study explores dog plasma and brain fatty acid composition achieved after long-term supplementation at high DHA doses. A 90% concentrate of DHA Ethyl Ester (DHA-EE) administered by oral gavage to Beagle dogs at doses of 100, 500, 1000, and 2000mg/kg bw/day for 8 weeks resulted in DHA increases in both plasma and brain. In a subsequent 9-month study, DHA-EE was administered at 150, 1000 and 2000mg/kg bw/day. Plasma DHA increased between 150 and 1000mg/kg bw/day but not between 1000 and 2000mg/kg bw/day and there were increases from Day 1to 92 but not between days 92 and 273. Doses >500mg/kg bw/day in the 8-week and all doses in the 9-month study resulted in DHA increases in the brain. The dose of 150mg/k gbw/day is sufficient to achieve maximal brain concentrations if DHA is administered chronically. For shorter than 6 months of supplementation, higher doses are required.