Oxidomics on the omega-3 volatile degradation pattern to determine differences between vegetable and marine oils.

In this work, oxidation assessment of vegetable and marine oils was performed based on their quantitative volatile profile and data analysis by 3-way partial least square chemometrics. Classification models were obtained using broad-spectrum isotopically labelled standards on the analysis of 25 volatile compounds from omega-3 fatty acid (FA) degradation by headspace solid phase microextraction gas chromatography time-of-flight mass spectrometry. Our oxidomic approach was performed on edible oils that differed in their origin (marine or vegetable) and in their omega-3 FA profile. In order to achieve a 3D matrix, every oil was oxidized at 6 different time-points. The obtained models classified edible oils according to their volatile degradation pattern. Oxidation of eicosapentaenoic/docosahexaenoic FA was mainly related to 2-propenal, butanal and 2-ethylfuran while α-linolenic acid oxidation was linked to 1-hydroxy-2-butanone and 5-ethyl-2(5H)-furanone. The present research provides valuable information on the degradation differences of omega-3 oils and proposes specific oxidation markers that could be used to ensure their quality assurance and avoid intentional adulterations.

Tandem Mass Tag Based Quantitative Proteomics of Developing Sea Buckthorn Berries Reveals Candidate Proteins Related to Lipid Metabolism.

Sea buckthorn ( Hippophae L.) is an economically important shrub or small tree distributed in Eurasia. Most of its well-recognized medicinal and nutraceutical products are derived from its berry oil, which is rich in monounsaturated omega-7 (C16:1) fatty acid and polyunsaturated omega-6 (C18:2) and omega-3 (C18:3) fatty acids. In this study, tandem mass tags (TMT)-based quantitative analysis was used to investigate protein profiles of lipid metabolism in sea buckthorn berries harvested 30, 50, and 70 days after flowering. In total, 8626 proteins were identified, 6170 of which were quantified. Deep analysis results for the proteins identified and related pathways revealed initial fatty acid accumulation during whole-berry development. The abundance of most key enzymes involved in fatty acid and triacylglycerol (TAG) biosynthesis peaked at 50 days after flowering, but TAG synthesis through the PDAT (phospholipid: diacylglycerol acyltransferase) pathway mostly occurred early in berry development. In addition, the patterns of proteins involved in lipid metabolism were confirmed by combined quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and parallel reaction monitoring analyses. Our data on the proteomic spectrum of sea buckthorn berries provide a scientific basic for understanding lipid metabolism and related pathways in the developing berries.

Omega-6 and omega-3 oxylipins are implicated in soybean oil-induced obesity in mice.

Soybean oil consumption is increasing worldwide and parallels a rise in obesity. Rich in unsaturated fats, especially linoleic acid, soybean oil is assumed to be healthy, and yet it induces obesity, diabetes, insulin resistance, and fatty liver in mice. Here, we show that the genetically modified soybean oil Plenish, which came on the U.S. market in 2014 and is low in linoleic acid, induces less obesity than conventional soybean oil in C57BL/6 male mice. Proteomic analysis of the liver reveals global differences in hepatic proteins when comparing diets rich in the two soybean oils, coconut oil, and a low-fat diet. Metabolomic analysis of the liver and plasma shows a positive correlation between obesity and hepatic C18 oxylipin metabolites of omega-6 (ω6) and omega-3 (ω3) fatty acids (linoleic and α-linolenic acid, respectively) in the cytochrome P450/soluble epoxide hydrolase pathway. While Plenish induced less insulin resistance than conventional soybean oil, it resulted in hepatomegaly and liver dysfunction as did olive oil, which has a similar fatty acid composition. These results implicate a new class of compounds in diet-induced obesity-C18 epoxide and diol oxylipins.

Cytochrome P450 2C8 ω3-long-chain polyunsaturated fatty acid metabolites increase mouse retinal pathologic neovascularization--brief report.

OBJECTIVE: Regulation of angiogenesis is critical for many diseases. Specifically, pathological retinal neovascularization, a major cause of blindness, is suppressed with dietary ω3-long-chain polyunsaturated fatty acids (ω3LCPUFAs) through antiangiogenic metabolites of cyclooxygenase and lipoxygenase. Cytochrome P450 epoxygenases (CYP2C8) also metabolize LCPUFAs, producing bioactive epoxides, which are inactivated by soluble epoxide hydrolase (sEH) to transdihydrodiols. The effect of these enzymes and their metabolites on neovascularization is unknown. APPROACH AND RESULTS: The mouse model of oxygen-induced retinopathy was used to investigate retinal neovascularization. We found that CYP2C (localized in wild-type monocytes/macrophages) is upregulated in oxygen-induced retinopathy, whereas sEH is suppressed, resulting in an increased retinal epoxide:diol ratio. With a ω3LCPUFA-enriched diet, retinal neovascularization increases in Tie2-driven human-CYP2C8-overexpressing mice (Tie2-CYP2C8-Tg), associated with increased plasma 19,20-epoxydocosapentaenoic acid and retinal epoxide:diol ratio. 19,20-Epoxydocosapentaenoic acids and the epoxide:diol ratio are decreased with overexpression of sEH (Tie2-sEH-Tg). Overexpression of CYP2C8 or sEH in mice does not change normal retinal vascular development compared with their wild-type littermate controls. The proangiogenic role in retina of CYP2C8 with both ω3LCPUFA and ω6LCPUFA and antiangiogenic role of sEH in ω3LCPUFA metabolism were corroborated in aortic ring assays. CONCLUSIONS: Our results suggest that CYP2C ω3LCPUFA metabolites promote retinal pathological angiogenesis. CYP2C8 is part of a novel lipid metabolic pathway influencing retinal neovascularization.

Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid?

BACKGROUND: A growing number of observational and epidemiological studies have suggested that mental illness, in particular mood disorders, is associated with reduced dietary intake and/or cellular abundance of omega-3 polyunsaturated fatty acids (PUFA). This has prompted researchers to test the efficacy of omega-3 PUFA in a range of different psychiatric disorders. We have critically reviewed the double blind placebo controlled clinical trials published prior to April 2007 to determine whether omega-3 PUFA are likely to be efficacious in these disorders. RESULTS: Most trials involved a small number of participants but were largely well designed. Omega-3 PUFA were well tolerated by both children and adults with mild gastrointestinal effects being the only consistently reported adverse event. For schizophrenia and borderline personality disorder we found little evidence of a robust clinically relevant effect. In the case of attention deficit hyperactivity disorder and related disorders, most trials showed at most small benefits over placebo. A limited meta-analysis of these trials suggested that benefits of omega-3 PUFA supplementation may be greater in a classroom setting than at home. Some evidence indicates that omega-3 PUFA may reduce symptoms of anxiety although the data is preliminary and inconclusive. The most convincing evidence for beneficial effects of omega-3 PUFA is to be found in mood disorders. A meta-analysis of trials involving patients with major depressive disorder and bipolar disorder provided evidence that omega-3 PUFA supplementation reduces symptoms of depression. Furthermore, meta-regression analysis suggests that supplementation with eicosapentaenoic acid may be more beneficial in mood disorders than with docosahexaenoic acid, although several confounding factors prevented a definitive conclusion being made regarding which species of omega-3 PUFA is most beneficial. The mechanisms underlying the apparent efficacy of omega-3 PUFA in mood disorders compared to schizophrenia are discussed as is a rational for the possibly greater efficacy of EPA compared to DHA. CONCLUSION: While it is not currently possible to recommend omega-3 PUFA as either a mono- or adjunctive-therapy in any mental illness, the available evidence is strong enough to justify continued study, especially with regard to attentional, anxiety and mood disorders.

Differentiating prescription omega-3-acid ethyl esters (P-OM3) from dietary-supplement omega-3 fatty acids.

BACKGROUND: A reliable means of treating hyper-triglyceridemia is the use of large doses of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Modest levels of EPA and DHA may be obtained from food, particularly fatty fish. OBJECTIVES: This article is intended to review clinically relevant differences between dietary-supplement omega-3 fatty acids and prescription omega-3-acid ethyl esters (P-OM3). METHODS: PubMed and the Food and Drug Administration (FDA) Website were searched for articles published between 1995 and 2007 that contained the terms fish oil, fatty acids, n-3 fatty acids, omega fatty acids, docosahexaenoic acid, or eicosapentaenoic acid. Articles discussing sources, recommended intake, and differences among various formulations of omega-3 fatty acids were selected for review. A limitation to this review is the lack of head-to-head clinical trials using P-OM3 and dietary-supplement omega-3 fatty acids. RESULTS: Many types of nonprescription dietary supplements of omega-3 fatty acids are available; however, the efficacy, quality, and safety of these products are open to question because they are not regulated by the same standards as pharmaceutical agents. P-OM3 is the only omega-3 fatty acid product (Omacor capsules) approved by the US FDA available in the United States as an adjunct to diet to reduce very high (> or = 500 mg/dL) triglyceride levels in adult patients. CONCLUSIONS: P-OM3 can be used with confidence by practitioners who want to provide therapeutic doses of omega-3 fatty acids in a preparation that has been documented to be both safe and effective.

Omega-3 fatty acids in the treatment of psychiatric disorders.

The importance of omega-3 fatty acids for physical health is now well recognised and there is increasing evidence that omega-3 fatty acids may also be important to mental health. The two main omega-3 fatty acids in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have important biological functions in the CNS. DHA is a major structural component of neuronal membranes, and changing the fatty acid composition of neuronal membranes leads to functional changes in the activity of receptors and other proteins embedded in the membrane phospholipid. EPA has important physiological functions that can affect neuronal activity. Epidemiological studies indicate an association between depression and low dietary intake of omega-3 fatty acids, and biochemical studies have shown reduced levels of omega-3 fatty acids in red blood cell membranes in both depressive and schizophrenic patients. Five of six double-blind, placebo-controlled trials in schizophrenia, and four of six such trials in depression, have reported therapeutic benefit from omega-3 fatty acids in either the primary or secondary statistical analysis, particularly when EPA is added on to existing psychotropic medication. Individual clinical trials have suggested benefits of EPA treatment in borderline personality disorder and of combined omega-3 and omega-6 fatty acid treatment for attention-deficit hyperactivity disorder. The evidence to date supports the adjunctive use of omega-3 fatty acids in the management of treatment unresponsive depression and schizophrenia. As these conditions are associated with increased risk of coronary heart disease and diabetes mellitus, omega-3 fatty acids should also benefit the physical state of these patients. However, as the clinical research evidence is preliminary, large, and definitive randomised controlled trials similar to those required for the licensing of any new pharmacological treatment are needed.