Synthesis of two new lipid mediators from docosahexaenoic acid by combinatorial catalysis involving enzymatic and chemical reaction.

Omega-3 polyunsaturated fatty acids (PUFAs) have been known to have beneficial effects in the prevention of various diseases. Recently, it was identified that the bioactivities of omega-3 are related to lipid mediators, called pro-resolving lipid mediators (SPMs), converted from PUFAs, so they have attracted much attention as potential pharmaceutical targets. Here, we aimed to build an efficient production system composed of enzymatic and chemical catalysis that converts docosahexaenoic acid (DHA) into lipid mediators. The cyanobacterial lipoxygenase, named Osc-LOX, was identified and characterized, and the binding poses of enzyme and substrates were predicted by ligand docking simulation. DHA was converted into three lipid mediators, a 17S-hydroxy-DHA, a 7S,17S-dihydroxy-DHA (RvD5), and a 7S,15R-dihydroxy-16S,17S-epoxy-DPA (new type), by an enzymatic reaction and deoxygenation. Also, two lipid mediators, 7S,15R,16S,17S-tetrahydroxy-DPA (new type) and 7S,16R,17S-trihydroxy-DHA (RvD2), were generated from 7S,15R-dihydroxy-16S,17S-epoxy-DPA by a chemical reaction. Our study suggests that discovering new enzymes that have not been functionally characterized would be a powerful strategy for producing various lipid mediators. Also, this combination catalysis approach including biological and chemical reactions could be an effective production system for the manufacturing lipid mediators.

Impact of cooked functional meat enriched with omega-3 fatty acids and rosemary extract on inflammatory and oxidative status; A randomised, double-blind, crossover study / Impacto de la carne funcional cocinada enriquecida con ácidos grasos omega 3 y extracto de romero sobre el estado inflamatorio y oxidativo; un estudio aleatorizado, cruzado y doble ciego

Background & Aim: n-3 fatty acid intake has been associated with inflammatory benefits in cardiovascular disease (CVD). Functionalising meat may be of great interest. The aim of the present study was to assess the effect of functional meat containing n-3 and rosemary extract on inflammatory and oxidative status markers in subjects with risk for CVD. Methods and results: A randomised, double-blind, cross-over study was undertaken to compare the effectson the above markers of consuming functional or control meat products. 43 volunteers with at least two lipid profile variables showing risk for CVD were randomly assigned to receive functional meat (FM) or control meat (CM) over 12-weeks with a 4-week wash-out interval before crossover. Functional effects were assessed by examining lipid profile, CRP, PAI-1, TNF-alpha, IL-6, fibrinogen (inflammatory markers), and TBARS, FRAP and 8-iso-PGF2α (oxidative status markers). 33 subjects (24 women) aged 50.7±8.8 years completed the study. In FM treatment, PAI-1, fibrinogen and 8-iso-PGF2α decreased significantly after 12 weeks, while FRAP significantly increased. In contrast, in CM treatment, a significant increase was seen in PAI-1, while FRAP significantly declined. Significant differences were also seen between the FM and CM treatments after 12 weeks in terms of the change observed in PAI-1, FRAP and8-iso-PGF2α values. No significant differences were seen in anthropometric variables nor were adverse effects reported. Conclusion: The consumption of FM containing n-3 and rosemary extract improved oxidative and inflammatory status of people with at least two lipid profile variables showing risk for CVD. The inclusion of such functional meat in a balanced diet might be a healthy lifestyle option (AU)

Objetivos: La ingesta de omega-3 se ha asociado con efectos antinflamatorios relacionados con la prevención de la enfermedad cardiovascular (ECV). Desarrollar productos cárnicos funcionales podría ser de gran interés para la población. El objetivo del presente estudio fue evaluar el efecto de una carne funcional con omega-3 y extracto de romero sobre marcadores de inflamación y oxidación en personas con riesgo cardiovascular. Pacientes y métodos: Se diseñó un ensayo clínico cruzado y doble-ciego para estudiar el efecto del consumo de un producto cárnico funcional sobre marcadores de inflamación y oxidación. Se incluyeron 43 voluntarios con al menos 2 parámetros del perfil lipídico alterado, indicando riesgo de ECV. Fueron asignados aleatoriamente en 2 grupos que consumieron en cruzado carne funcional (CF) o carne control (CC) durante 12 semanas con un periodo de lavado de 4 semanas entre ellos. Al finalizar el estudio se evaluó: perfil lipídico, marcadores de inflamación (PCR, PAI-1, TNF-alpha, IL-6, fibrinógeno) ymarcadores de oxidación (TBARS, FRAP, 8-iso-PGF2α). Resultados: Completaron el estudio 33 personas (24 mujeres) con edad media de 50.7±8.8 años. Tras consumir CF durante 12 semanas se observó una disminución significativa del PAI-1, fibrinógeno y 8-iso-PGF2α, mientras que el FRAP incrementó significativamente. Sin embargo, con CC incrementó PAI-1 y disminuyó FRAP significativamente. Además se observaron diferencias significativas entre los cambios producidos tras consumir uno u otro producto de los marcadores PAI-1, FRAP y 8-iso-PGF2α. Al final de cada intervención no se observaron cambios en variables antropométricas ni efectos adversos. Conclusiones: El consumo de CF con omega-3 y extracto de romero mejora el estado inflamatorio y oxidativo de personas con al menos 2 parámetros del perfil lipídico alterado. La inclusión de estas CF en una dieta equilibrada podría ser una opción más para mantener un estilo de vida saludable (AU)

Synthetic ω-3 epoxyfatty acids as antiproliferative and pro-apoptotic agents in human breast cancer cells.

ω-3-17,18-Epoxyeicosapentaenoic acid decreases cell proliferation and activates apoptosis, whereas its regioisomers stimulate growth. We evaluated synthetic ω-3 epoxides of saturated fatty acids as antiproliferative and pro-apoptotic agents in MDA-MB-231 breast cancer cells. The epoxides, but not their urea, amide, or carbamate isosteres, impaired ATP production, enhanced caspase-3 activity, and activated c-jun-N-terminal-kinase signaling, leading to cyclin D1 down-regulation and cell cycle arrest in G1-phase. Fatty acid ω-3 monoepoxides may represent a novel class of antitumor agents.

Dietary n-3 polyunsaturated fatty acids and the paradox of their health benefits and potential harmful effects.

There is some evidence to support the toxicity of polyunsaturated fatty acids (PUFAs) and their oxidative products, suggesting their involvement in the pathogenesis of different chronic diseases, including cancer. It has been shown that products of PUFA oxidation may exert a carcinogenic action by forming mutagenic adducts with DNA. However, a large amount of evidence accumulated over several decades has indicated the beneficial effects of administration of n-3 PUFAs in the prevention and therapy of a series of diseases. In particular, there is much evidence that n-3 PUFAs exert anti-inflammatory and antineoplastic effects, whereas n-6 PUFAs promote inflammation and carcinogenesis. In our tissues, both of the two classes of PUFAs can be converted into bioactive products, incorporated into membrane phospholipids or bound to membrane receptors, where they may alter, often in opposite ways, transduction pathways and affect important biological processes, such as cell death and survival, inflammation, and neo-angiogenesis. In the present review, we intend to shed light on the paradox of the coexisting healthy and toxic effects of n-3 PUFAs, focusing on their possible pro-oxidant cytotoxic and carcinogenic effect, in order to understand if their increased intake, recommended by a number of health agencies worldwide and promoted by nutraceutical producers, may or may not represent a hazard to human health.

Omega-3 fatty acids in food and pharma: the enabling role of biotechnology.

Omega-3 fatty acid research, which began as an epidemiologic curiosity, has generated perhaps the strongest dataset for any nutrient in regard to cardiovascular disease risk reduction. Although once a relatively descriptive field, advances in analytic techniques have opened up the biochemistry of omega-3 fatty acids and nutritional genomics in plants and man and have taken the field into the "omic" era. Despite this progress, fundamental questions remain unanswered, such as which fatty acid or metabolite thereof drives a given health benefit, how much of a given fatty acid should we consume, and how do we best source the requisite fatty acids? Of these questions, the ability to source omega-3 fatty acids in order to meet dietary guidelines has become a practical concern. The advent of novel oils from plants and single cell organisms as enabled by biotechnology may provide a solution to this problem and in the process open up new uses for omega-3 fatty acids in dietary supplements and drugs.

El papel de los ácidos grasos n-3: estudios clínicos / No disponible

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