Stearidonic-Enriched Soybean Oil Modulates Obesity, Glucose Metabolism, and Fatty Acid Profiles Independently of Akkermansia muciniphila.

SCOPE: Previous studies have suggested that diets rich in omega-3 and low in omega-6 long-chain polyunsaturated fatty acids (PUFAs) can limit the development of metabolic syndrome (MetS). Transgenic soybeans yielding oils enriched for omega-3 PUFAs represent a new and readily-available option for incorporating omega-3 PUFAs into diets to provide health benefits. METHODS AND RESULTS: Transgenic soybean oils, enriched for either stearidonic acid (SDA) or eicosapentaenoic acid (EPA), are incorporated into diets to test their effects on limiting the development of MetS in a mouse model of diet-induced obesity. Supplementation with SDA- but not EPA-enriched oils improved features of MetS compared to feeding a control wild-type oil. Because previous studies have linked the gut microorganism Akkermansia muciniphila to the metabolic effects of feeding omega-3 PUFAs, the causal contribution of A. muciniphila to mediating the metabolic benefits provided by SDA-enriched diets is investigated. Although A. muciniphila is not required for SDA-induced metabolic improvements, this microorganism does modulate levels of saturated and mono-unsaturated fatty acids in host adipose tissues. CONCLUSION: Together, these findings support the utilization of SDA-enriched diets to modulate weight gain, glucose metabolism, and fatty acid profiles of liver and adipose tissue.

Bioavailable phytoprostanes and phytofurans from Gracilaria longissima have anti-inflammatory effects in endothelial cells.

BACKGROUND: An array of bioactive compounds with health-promoting effects has been described in several species of macroalgae. Among them, phytoprostanes (PhytoPs) and phytofurans (PhytoFs), both autoxidation products of α-linolenic acid, have been seen to exert immunomodulatory and antiinflammatory activities in vitro. The purpose of this study was to explore the bioaccesibility, bioavailability, and bioactivity of PhytoPs and PhytoFs obtained from the edible red algae Gracilaria longissima, and to gain insight into the anti-inflammatory activity of their bioavailable fraction in human endothelial cells. METHODS: The PhytoPs and PhytoFs profile and concentration of G. longissima were determined by UHPLC-QqQ-MS/MS. Algal samples were processed following a standardised digestion method including gastric, intestinal, and gastrointestinal digestion. The bioavailability of the PhytoPs and PhytoFs in the characterized fractions was assessed in a Caco-2 cell monolayer model of the intestinal barrier. The inflammation response of these prostaglandin-like compounds in human endothelial cells, after intestinal absorption, was investigated in vitro. RESULTS: Simulated digestions significantly reduced the concentration of PhytoPs and PhytoFs up to 1.17 and 0.42 µg per 100 g, respectively, on average, although permeability through the Caco-2 cell monolayer was high (up to 88.2 and 97.7%, on average, respectively). PhytoP and PhytoF-enriched extracts of raw algae impaired the expression of ICAM-1 and IL-6 inflammation markers. The inflammation markers progressed in contrast to the relative concentrations of bioactive oxylipins, suggesting pro- or anti-inflammatory activity on their part. In this aspect, the cross-reactivity of these compounds with diverse receptors, and their relative concentration could explain the diversity of the effects found in the current study. CONCLUSIONS: The results indicate that PhytoPs and PhytoFs display complex pharmacological profiles probably mediated through their different actions and affinities in the endothelium.

Simulated in vitro infant gastrointestinal digestion of yak milk fat globules: A comparison with cow milk fat globules.

Lipolysis products released during digestion exert positive metabolic impacts on the nutrition of newborns. However, the lipolysis behavior of yak milk lipids during digestion remains unknown. In this study, the simulated in vitro infant gastrointestinal digestion of cow, yak and standardized yak milk fat globules the same size as those from cow milk (Cow MF, Yak MF and Yak SMF) were compared. Although Cow MF showed a higher lipolysis rate at the beginning of gastric digestion, Yak MF and Yak SMF exhibited a higher lipolysis level during later gastrointestinal digestion. Higher hydrolysis efficiency of yak milk lipids was due to their lipid properties, including their composition and structure. Furthermore, yak milk lipids released more unsaturated fatty acids than Cow MF throughout digestion. This study highlights the crucial role of lipid characteristics in the efficient digestion of milk lipids and provides new insight for the design of yak milk infant diets.

A Randomized, Placebo-Controlled, Double-Blind, Dose Escalation, Single Dose, and Steady-State Pharmacokinetic Study of 9cUAB30 in Healthy Volunteers.

9cUAB30 is a synthetic analogue of 9-cis retinoic acid with chemoprevention activity in cell lines and animal models. The purpose of this phase I placebo-controlled, double-blinded, dose escalation study of 9cUAB30 was to evaluate its safety, pharmacokinetics, and determine a dose for future phase II studies. Participants received a single dose of study drug (placebo or 9cUAB30) on day 1 followed by a 6-day drug-free period and then 28 days of continuous daily dosing starting on day 8. Fifty-three healthy volunteers were enrolled into five dose cohorts (20, 40, 80, 160, and 240 mg). Participants were randomized within each dose level to receive either 9cUAB30 (n = 8) or placebo (n = 2). 9cUAB30 was well tolerated, with no dose limiting toxicities reported and no evidence of persistent elevations in serum triglycerides or cholesterol. Treatment-emergent grade 3 hypertension occurred in 1 of 8 participants at the 20 mg dose level and in 2 of 8 at the 240 mg dose level, all considered unlikely related to study agent; no other grade 3 adverse events were observed. The AUC increased, as expected, between day 1 (single dose) and day 36 (steady state). Pharmacokinetics were linear in dose escalation through 160 mg. 9cUAB30 administered by daily oral dosing has a favorable safety and pharmacokinetic profile. On the basis of the observed safety profile and lack of linearity in pharmacokinetics at doses greater than 160 mg, the recommended phase II dose with the current formulation is 160 mg once daily.

Effects of nano-sizing on lipid bioaccessibility and ex vivo bioavailability from EPA-DHA rich oil in water nanoemulsion.

The physiological efficacy of nutraceuticals is dependent on their physicochemical nature and bioavailability across biological barriers. In the present work, effects of nano-sizing of emulsion-based delivery vehicle on the bioavailability of polyunsaturated fatty acids rich fish oil have been investigated via three-step experimental design; ex vivo rat everted intestinal sac model, cellular lipid uptake and the bioactivity in rat PBMCs. Nanoemulsion in comparison to the conventional emulsion has shown significant higher rate of uptake of polyunsaturated fatty acids in three segments of small intestine. The time-kinetics of such uptake was correlated with appearance of short-chain fatty acids in basal side of the everted sac. The bioavailability of the formulated fish oil and its inhibitory response against lipopolysaccharide-induced nitric oxide production in rat PBMCs were positively correlated. This formulation with nano-sized droplets can be utilized as smart delivery vehicles for designing oral therapies in future.

Fitness for purpose and stability assessment of long-chain polyunsaturated fatty acids in chicken tissues.

The global popularity of chicken in human diets make it an obvious choice for enrichment with DHA and LC-PUFA. There is presently a need for a robust method for the analysis of chicken tissues and where the fitness for purpose of the method has been demonstrated. The purpose of this paper is to present the validation of the AOAC method 996.06 on five different chicken tissues; breast, thigh, skin, kidney and liver. The parameters investigated as part of the validation study included; linearity and range, the limit of detection and limit of quantification, accuracy, repeatability, inter-analyst reproducibility, and specificity. The method was further applied to assess the stability of DHA and other specific LC-PUFA in chicken tissues over short and long timepoints. The disclosure of this information is relevant for researchers concerned with the analysis of LC-PUFA in regulatory and efficacy studies.

Cytotropic heterogeneous molecular lipids inhibit the growth of glioma cells by inducing apoptosis and autophagy.

The cytotropic heterogeneous molecular lipid (CHML) is a mixture of lipids isolated from natural products. CHML is an effective therapy for various kinds of cancers; however, the effect of CHML on glioma cells was seldom reported. Here, we aim to explore the cytotoxicity of CHML on glioma cells, and analyze the possible mechanisms. U251 glioma cells were cultured with CHML at different concentration, and the growth inhibition was measured by CCK-8 assay. Induced apoptosis were detected by flow cytometry, and the induced autophagies were observed by a transmission electron microscope. The key molecules involved in apoptosis and autophagy were detected by quantitative PCR and western-blot. CHML might inhibit the growth of U251 cells and promote apoptosis by up-regulating the expressions of Caspase-8 and Caspase-3; CHML also induced autophagy of U251 cells by promoting the expressions of MAP LC-3 and Beclin-1. CHML can inhibit proliferation of U251 cells by promoting cell apoptosis and inducing autophagy.

Designing Natural Product Hybrids Bearing Triple Antiplatelet Profile and Evaluating Their Human Plasma Stability.

Cardiovascular diseases (CVDs) are becoming major contributors to the burden of disease due to genetic and environmental factors. Despite current standard oral care, cardiovascular risk remains relatively high. A triple antiplatelet therapy with a cyclooxygenase-1 (COX-1) inhibitor, a P2Y12 receptor antagonist, and a protease-activated receptor-1 (PAR-1) antagonist has been established in the secondary prevention of atherothrombosis in patients with acute myocardial infraction and in those with peripheral artery disease. However, due to the combinatorial use of three different drugs, patients receiving this triple therapy are exposed to enhanced risk of bleeding. Conforming to polypharmacology principles, the discovery of a single compound that can simultaneously block the three platelet activation pathways (PAR-1, P2Y12, and COX-1) is of importance. Natural products have served as an inexhaustible source of bioactive compounds presenting a diverse pharmaceutical profile, including anti-inflammatory, antioxidant, anticancer, and antithrombotic activity. Indeed, principal component analysis indicated that natural products have the potential to inhibit the three aforementioned pathways, though existed reports refer to single inhibition mechanism on specific receptor(s) implicated in platelet activation. We thus set out to explore possibilities that take advantage of this potential of natural products and shape the basis to produce novel compounds that could simultaneously target PAR-1, P2Y12, and COX-1 platelet activation pathways. Polyunsaturated fatty acids (PUFAs) have multiple effects leading to improvements in blood pressure and cardiac function and arterial compliance. A promising approach to achieve the desirable goal is the bioconjugation of natural products with PUFAs. Herein, we describe the principles that should be followed to develop molecular hybrids bearing triple antiplatelet activity profile.

The Role of n-3 Long Chain Polyunsaturated Fatty Acids in Cardiovascular Disease Prevention, and Interactions with Statins.

Decreases in global cardiovascular disease (CVD) mortality and morbidity in recent decades can be partly attributed to cholesterol reduction through statin use. n-3 long chain polyunsaturated fatty acids are recommended by some authorities for primary and secondary CVD prevention, and for triglyceride reduction. The residual risk of CVD that remains after statin therapy may potentially be reduced by n-3 long chain polyunsaturated fatty acids. However, the effects of concomitant use of statins and n-3 long chain polyunsaturated fatty acids are not well understood. Pleiotropic effects of statins and n-3 long chain polyunsaturated fatty acids overlap. For example, cytochrome P450 enzymes that metabolize statins may affect n-3 long chain polyunsaturated fatty acid metabolism and vice versa. Clinical and mechanistic study results show both synergistic and antagonistic effects of statins and n-3 long chain polyunsaturated fatty acids when used in combination.

All n-3 PUFA are not the same: MD simulations reveal differences in membrane organization for EPA, DHA and DPA.

Eicosapentaenoic (EPA, 20:5), docosahexaenoic (DHA, 22:6) and docosapentaenoic (DPA, 22:5) acids are omega-3 polyunsaturated fatty acids (n-3 PUFA) obtained from dietary consumption of fish oils that potentially alleviate the symptoms of a range of chronic diseases. We focus here on the plasma membrane as a site of action and investigate how they affect molecular organization when taken up into a phospholipid. All atom MD simulations were performed to compare 1-stearoyl-2-eicosapentaenoylphosphatylcholine (EPA-PC, 18:0-20:5PC), 1-stearoyl-2-docosahexaenoylphosphatylcholine (DHA-PC, 18:0-22:6PC), 1-stearoyl-2-docosapentaenoylphosphatylcholine (DPA-PC, 18:0-22:5PC) and, as a monounsaturated control, 1-stearoyl-2-oleoylphosphatidylcholine (OA-PC, 18:0-18:1PC) bilayers. They were run in the absence and presence of 20mol% cholesterol. Multiple double bonds confer high disorder on all three n-3 PUFA. The different number of double bonds and chain length for each n-3 PUFA moderates the reduction in membrane order exerted (compared to OA-PC, S¯CD=0.152). EPA-PC (S¯CD=0.131) is most disordered, while DPA-PC (S¯CD=0.140) is least disordered. DHA-PC (S¯CD=0.139) is, within uncertainty, the same as DPA-PC. Following the addition of cholesterol, order in EPA-PC (S¯CD=0.169), DHA-PC (S¯CD=0.178) and DPA-PC (S¯CD=0.182) is increased less than in OA-PC (S¯CD=0.214). The high disorder of n-3 PUFA is responsible, preventing the n-3 PUFA-containing phospholipids from packing as close to the rigid sterol as the monounsaturated control. Our findings establish that EPA, DHA and DPA are not equivalent in their interactions within membranes, which possibly contributes to differences in clinical efficacy.

Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.

In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting.

Quantitative In Vitro and In Vivo Evaluation of Intestinal and Blood-Brain Barrier Transport Kinetics of the Plant N-Alkylamide Pellitorine.

Objective. To evaluate the gut mucosa and blood-brain barrier (BBB) pharmacokinetic permeability properties of the plant N-alkylamide pellitorine. Methods. Pure pellitorine and an Anacyclus pyrethrum extract were used to investigate the permeation of pellitorine through (1) a Caco-2 cell monolayer, (2) the rat gut after oral administration, and (3) the BBB in mice after intravenous and intracerebroventricular administration. A validated bioanalytical UPLC-MS(2) method was used to quantify pellitorine. Results. Pellitorine was able to cross the Caco-2 cell monolayer from the apical-to-basolateral and from the basolateral-to-apical side with apparent permeability coefficients between 0.6 · 10(-5) and 4.8 · 10(-5) cm/h and between 0.3 · 10(-5) and 5.8 · 10(-5) cm/h, respectively. In rats, a serum elimination rate constant of 0.3 h(-1) was obtained. Intravenous injection of pellitorine in mice resulted in a rapid and high permeation of pellitorine through the BBB with a unidirectional influx rate constant of 153 µL/(g·min). In particular, 97% of pellitorine reached the brain tissue, while only 3% remained in the brain capillaries. An efflux transfer constant of 0.05 min(-1) was obtained. Conclusion. Pellitorine shows a good gut permeation and rapidly permeates the BBB once in the blood, indicating a possible role in the treatment of central nervous system diseases.

Unsaturated fatty acids lactose esters: cytotoxicity, permeability enhancement and antimicrobial activity.

Sugar based surfactants conjugated with fatty acid chains are an emerging broad group of highly biocompatible and biodegradable compounds with established and potential future applications in the pharmaceutical, cosmetic and food industries. In this work, we investigated absorption enhancing and antimicrobial properties of disaccharide lactose, monoesterified with unsaturated fatty acids through an enzymatic synthetic approach. After chemical and cytotoxicity characterizations, their permeability enhancing activity was demonstrated using intestinal Caco-2 monolayers through transepithelial electrical resistance (TEER) and permeability studies. The synthesized compounds, namely lactose palmitoleate (URB1076) and lactose nervonate (URB1077), were shown to exhibit antimicrobial activity versus eight pathogenic species belonging to Gram-positive, Gram-negative microorganisms and fungi.

Bioavailability of long chain omega-3 polyunsaturated fatty acids from phospholipid-rich herring roe oil in men and women with mildly elevated triacylglycerols.

This randomized, single-blind, crossover trial assessed the bioavailability of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) from two different sources, each examined over a 12h period following consumption of a single serving and after 2-weeks of daily supplementation. Thirty-two adults with fasting triacylglycerol (TAG) concentrations between 100 and 399mg/dL were randomly assigned, with stratification by sex and age, to receive 12 capsules/day containing either phospholipid (PL)-rich herring roe oil (Romega® 30, 628mg/day EPA; 1810mg/day DHA; 137mg/day DPA) or TAG-rich fish oil (575mg/day EPA; 1843mg/day DHA; 259mg/day DPA) each for a 2-week period separated by a 4 week washout. The net incremental area under the curve from 0 to 12h for EPA, DHA, and EPA+DHA in plasma phosphatidylcholine (PC) were significantly higher (p<0.01 for all) after Romega 30 supplementation compared to fish oil. Similar results were observed when the data for the Romega 30 condition were normalized to fish oil EPA and DHA intakes (p<0.001 for all). After the 2-week supplementation period, fasting plasma PC EPA+ DHA was elevated by ~2.8 to 3.0-fold relative to baseline in both conditions (p<0.0001 for each), but there was no significant difference in the change from baseline (p=0.422) between Romega 30 (baseline=62.2±3.8µg/mL vs. end of study=172.9±11.7µg/mL) and fish oil (baseline=62.0±3.4µg/mL vs. end of study=185.4±11.2µg/mL) conditions. Similar results were observed for each individual LC n-3 PUFA in plasma PC after 2 weeks of supplementation. These data demonstrate that PL-rich herring roe is a well-tolerated and bioavailable source of LC n-3 PUFA.

A method for quantification of exportin-1 (XPO1) occupancy by Selective Inhibitor of Nuclear Export (SINE) compounds.

Selective Inhibitor of Nuclear Export (SINE) compounds are a family of small-molecules that inhibit nuclear export through covalent binding to cysteine 528 (Cys528) in the cargo-binding pocket of Exportin 1 (XPO1/CRM1) and promote cancer cell death. Selinexor is the lead SINE compound currently in phase I and II clinical trials for advanced solid and hematological malignancies. In an effort to understand selinexor-XPO1 interaction and to establish whether cancer cell response is a function of drug-target engagement, we developed a quantitative XPO1 occupancy assay. Biotinylated leptomycin B (b-LMB) was utilized as a tool compound to measure SINE-free XPO1. Binding to XPO1 was quantitated from SINE compound treated adherent and suspension cells in vitro, dosed ex vivo human peripheral blood mononuclear cells (PBMCs), and PBMCs from mice dosed orally with drug in vivo. Evaluation of a panel of selinexor sensitive and resistant cell lines revealed that resistance was not attributed to XPO1 occupancy by selinexor. Administration of a single dose of selinexor bound XPO1 for minimally 72 hours both in vitro and in vivo. While XPO1 inhibition directly correlates with selinexor pharmacokinetics, the biological outcome of this inhibition depends on modulation of pathways downstream of XPO1, which ultimately determines cancer cell responsiveness.

Bioactive substances with preventive effect in cardiovascular diseases / Sustancias bioactivas con efecto preventivo en la enfermedad cardiovascular

The effect of diet on cardiovascular disease prevention has been widely studied for many years. Numerous studies have confirmed that diets rich in fruits and vegetables (Mediterranean diet) are beneficial to the cardiovascular system and various bioactive food components have preventive effect on chronic diseases such as cardiovascular disease. In this paper we review the effect of bioactive substances included in the group of flavonoids (catechins and proanthocyanidins, anthocyanins and isoflavones), stilbenes such as resveratrol, bioactive peptides, plant sterols and polyunsaturated fatty acids omega-3 on the cardiovascular system (AU)

El efecto de la dieta sobre la prevención de las enfermedades cardiovasculares ha sido ampliamente estudiado durante muchos años. Numerosos estudios han corroborado que las dietas ricas en frutas y hortalizas (dieta mediterránea) resultan cardiosaludables y que diversas sustancias bioactivas que componen los alimentos tienen un efecto preventivo en diversas enfermedades crónicas como son las enfermedades cardiovasculares. En esta revisión vamos a tratar ciertas sustancias bioactivas, como son algunas incluidas en el grupo de los flavonoides (catequinas y proantocianidinas, antocianinas e isoflavonas), estilbenos como el resveratrol, péptidos bioactivos, esteroles vegetales y ácidos grasos poliinsaturados omega-3 (AU)

Dietary ratios of n-6/n-3 polyunsaturated fatty acids during maternal pregnancy affect hippocampal neurogenesis and apoptosis in mouse offspring / Las ratios nutricionales de ácidos grasos poliinsaturados n-6/n-3 durante la gestación afectan a la neurogénesis hipocampal y a la apoptosis en las crías de ratones

Objective: although n-3 polyunsaturated fatty acids (PUFAs) play crucial roles in brain development and function, neither the optimal level of n-3 PUFAs nor the optimal ratio of n-6/n-3 PUFAs in the maternal diet are well defined. In this study, we investigated the effects of dietary n-6/n-3 PUFA ratios during pregnancy on neurogenesis and apoptosis in the brains of mouse offspring. Metods: female C57BL/6J mice were fed one of three diets with high, medium and low ratios of n-6/n-3 PUFAs (15.7:1, 6.3:1, 1.6:1), as well as a high fish oil diet with a n-6/n-3 ratio of 1:5.7; an n-3 PUFA-deficient diet served as control. The feeding regimens began two months before mouse conception and continued for the duration of the pregnancy. The neurogenesis and apoptosis of hippocampal CA3 area in the offspring were detected. Results: compared to the n-3 PUFA-deficient diet, n-3 PUFA-containing diets, particularly those with n-6/n-3 PUFA ratios of 6.3:1 and 1.6:1, significantly increased both phosphorylation of histone H3 at ser 10 (p-H3ser10) and calretinin-positive cells in hippocampus CA3 of the offspring. Furthermore, increased expression of Bcl2 protein, decreased expression of Bax protein, and reduced caspase 3 activity and numbers of TUNEL apoptotic cells were found in the three diets with high, medium and low n-6/n-3 PUFA ratios. However, there were no differences in any of these parameters between the high fish oil diet group and the n-3 PUFA-deficient diet group. Conclusions: these data suggest that a higher intake of n-3 PUFAs with a lower ratio of n-6/n-3 PUFAs of between about 6:1 to 1:1, supplied to mothers during pregnancy, may benefit brain neurogenesis and apoptosis in offspring. However, excessive maternal intake of n-3 PUFAs may exert a negative influence on brain development in the offspring (AU)

Objetivo: a pesar de que los ácidos grasos poliinsaturados n-3 (PUFAs por sus siglas en inglés) desempeñan un papel fundamental en el desarrollo y en las funciones cerebrales, aún no está bien definido el nivel óptimo de PUFAs n-3 ni la ratio óptima de PUFA n-6/n-3 en la dieta materna. En este estudio hemos investigado los efectos de las ratios nutricionales de PUFA n-6/n-3 durante la gestación sobre la neurogénesis y la apoptosis en el cerebro de crías de ratón. Métodos: se alimentó a hembras de ratón C57BL/6J con una de las tres dietas de estudio: ratio alta, media y baja de PUFA n-6/n-3 (15,7:1, 6,3:1, 1,6:1). También se añadió una dieta rica en aceite de pescado con una ratio n-6/n-3 de 1:5,7; como control se empleó una dieta deficitaria en PUFA n-3. Los regímenes alimenticios se iniciaron dos meses antes de la concepción de los ratones y continuó durante todo el embarazo. Se detectó la neurogénesis y apoptosis del área hipocampal CA3 en las crías. Resultados: en comparación con la dieta deficitaria en PUFA n-3, las dietas con PUFA que contienen n-3, particularmente aquellas con ratios PUFA n-6/n-3 de 6,3:1 y 1,6:1, aumentaron significativamente la fosforilación de histona H3 en la Ser10 (p-H3ser10) y las células calretinina positivas en el área hipocampal CA3 de las crías. Además, se detectó un aumento de la expresión de proteí- na Bcl2, una reducción de la expresión de proteína Bax, y una reducción de la actividad de caspasa 3, así como de las cifras de células apoptósicas TUNEL en las tres dietas, con ratios altas, medias y bajas de PUFA n-6/n-3. Sin embargo, no se observó diferencias en ninguno de estos parámetros entre el grupo de dieta rica en aceite de pescado y el grupo de dieta deficitaria en PUFA n-3. Conclusiones: estos datos sugieren que una ingesta más elevada de PUFA n-3 con una ratio más baja de PUFAs n-6/n-3 entre 6:1 y 1:1 aproximadamente, administrada a las madres durante la gestación, podría ser beneficiosa para la neurogénesis cerebral y la apoptosis de las crías. Sin embargo, una ingesta excesiva de PUFA n-3 puede ejercer una influencia negativa sobre el desarrollo de las crías (AU)

Efecto de los ácidos grasos poliinsaturados en la prevención de la obesidad a través de modificaciones epigenéticas / The effect of polyunsaturated fatty acids on obesity through epigenetic modifications

ANTECEDENTES Y OBJETIVO: En los últimos años se ha demostrado que los ácidos grasos poliinsaturados (AGPI) tienen efectos antiinflamatorios y como reguladores del metabolismo lipídico. No obstante, no se conocen en profundidad los mecanismos epigenómicos implicados en estos procesos. El objetivo de esta revisión fue describir las evidencias científicas que apoyan que el consumo regular de AGPI puede reducir la obesidad mediante modificaciones de las marcas epigenéticas. MATERIAL Y MÉTODOS: Se realizó una búsqueda de publicaciones recientes llevadas a cabo en ensayos clínicos en humanos, modelos animales o ensayos in vitro. RESULTADOS: Existe un posible efecto terapéutico de los AGPI sobre la prevención y desarrollo de la obesidad gracias a su capacidad de modificar reversiblemente la metilación de los promotores de genes asociados con el metabolismo lipídico y de modular la actividad de determinados microARN. CONCLUSIONES: Los resultados publicados hasta la fecha referentes al rol de los AGPI en la prevención de la obesidad contribuyen al mejor conocimiento y entendimiento de las modificaciones epigenéticas de la obesidad. Los AGPI han demostrado poder modificar epigenéticamente diferentes genes adipogénicos mediante la metilación de sus promotores o mediante la regulación de su interacción con diversos microARN

BACKGROUND AND PURPOSE: In recent years it has been demonstrated that polyunsaturated fatty acids (PUFA) have anti-inflammatory and as regulators of lipid metabolism. However, the epigenomic mechanisms involved in these processes are not known in depth. The aim of this review was to describe the scientific evidence supports that regular consumption of PUFA may reduce obesity and overweight by altering epigenetic marks. MATERIAL AND METHODS: A search of recent publications was carried out in human clinical trials, as well as animal model and in vitro experiments. RESULTS: Exist a possible therapeutic effect of PUFAs on the prevention and development of obesity due to their ability to reversively modify the methylation of the promoters of genes associated with lipid metabolism and to modulate the activity of certain microRNAs. CONCLUSIONS: A better knowledge and understanding of the PUFAs role in epigenetic regulation of obesity is possible with the current published results. The PUFAs may modulate the promotor epigenetic marks in several adipogenic genes and regulate the expression of several miRNAs

Influencia de los ácidos grasos poliinsaturados en la prevención y promoción del cáncer / The influence of the polyunsaturated fatty acids in the prevention and promotion of cancer

Introducción: alrededor de ocho millones de personas mueren anualmente en el mundo debido al cáncer. La carcinogénesis es un proceso que conlleva, entre otras, una serie de alteraciones de la estructura del ADN, afectando su estabilidad e impidiendo la correcta proliferación celular. Son muchos los factores que influyen en la etiología del cáncer. Dentro de dichos factores están los nutricionales. La ingesta de ácidos grasos poliinsaturados (AGPI) se relaciona cada vez más con la prevención y el desarrollo de enfermedades crónicas con un componente inflamatorio, como el cáncer. Objetivo: revisar la bibliografía más reciente de los últimos cinco años sobre la ingesta de AGPI y su relación con el cáncer, principalmente de próstata, mama y colon, para concretar la posible existencia de una evidencia científica concluyente al respecto. Método: la búsqueda preliminar en la literatura proporcionó 92 referencias. Finalmente, tras su revisión, se han incluido 40 estudios directamente relacionados, conformados por estudios experimentales, en animales e in vitro, así como estudios epidemiológicos. Resultados: los estudios experimentales en animales e in vitro revisados concluyen un efecto protector de los AGPI omega-3 frente al cáncer. Sin embargo, los estudios en humanos son contradictorios, aunque sí parece existir una clara evidencia del efecto protector de los AGPI ω3 en la prevención del cáncer de colon. Conclusión: la relación entre AGPI ω6 y AGPI ω3 de la dieta frente al riesgo de padecer cáncer cobra cada vez más importancia, si bien se necesitan más estudios para confirmar su influencia en el desarrollo de esta enfermedad (AU)

Introduction: each year, almost eight million people die in the world due to cancer. Carcinogenesis is a process that involves a series of structural alterations of the DNA which affect its stability and prevents proper cell reproduction and development. There are many factors that influence the cancer etiology. Nutritional factors are included among them. The polyunsaturated fatty acids (PUFA) intake is associated more and more with the prevention and development of chronic diseases with an inflammatory component such as cancer. Objective: this work reviews the latest bibliography on the PUFA and its relationship with the cancer, mainly of prostate, breast and colon cancer. Methods: the preliminary search resulted in 92 selected references. But, after their review, 40 experimental studies, in animals and in vitro, and epidemiological studies have been included. Results: experimental studies in animals and in vitro reviewed show a protective effect of ω3 PUFA against cancer. However, human studies are contradictory; although it is clear there is evidence of the protective effect of the ω3 PUFA in colon cancer prevention. Conclusion: the relationship between ω6 and ω3 PUFA of the diet against the cancer risk is becoming increasingly important, but further studies are needed to confirm their influence on the development of this disease (AU)

Protection of polyunsaturated fatty acids against ruminal biohydrogenation: Pilot experiments for three approaches.

Three methods for protection of PUFA against biohydrogenation by ruminal microorganisms were evaluated. In method 1 a blend of ground flaxseed, calcium oxide, and molasses was processed through a dry extruder. In method 2, a blend of ground flaxseed, soybean meal, molasses, and baker's yeast was moistened and prewarmed, allowing enzymes from yeast to produce reducing sugars, and the mixture was subsequently processed through a dry extruder like in method 1. In method 3, ground flaxseed was embedded within a matrix of dolomitic lime hydrate (L-Flaxseed) as a protective barrier against biohydrogenation. Dolomitic lime was mixed with ground flaxseed, water was added, the mixture was blended in a high-speed turbulizer, and the resulting material was then dried to form a granular matrix. Methods 1 and 2 were tested in 1 study (study 1), and method 3 was tested in 2 studies (studies 2 and 3). In study 1, 60 crossbred yearling steers (BW = 475 ± 55 kg) were used in a randomized complete block design experiment. Steers were fed for 12 d with a diet consisting of 48.73% steam-flaked corn, 35% wet corn gluten feed, 12% corn silage, and 4.27% vitamins and minerals (Control). For the other 4 treatments, a portion of wet corn gluten feed was replaced with 5% of unprocessed or extruded mixtures as described for methods 1 and 2. Steers were weighed, and jugular blood samples were taken for analysis of long-chain fatty acids (LCFA) on d 0 and 12 of the study. Both methods failed to improve resistance of PUFA against biohydrogenation (P > 0.1). In study 2, in situ fatty acid disappearance was evaluated for ground flaxseed (Flaxseed) or L-Flaxseed using 6 ruminally fistulated Holstein steers. The proportion of α-linolenic acid (ALA) that was resistant to ruminal biohydrogenation was approximately 2-fold greater for L-Flaxseed than for Flaxseed (P < 0.05). In study 3, 45 steers (269 ± 19.5 kg initial BW) were used in a randomized complete block design. Steers were fed diets containing 0% Flaxseed (No Flaxseed), and in treatments 2 and 3, a portion of flaked corn was replaced with Flaxseed or L-Flaxseed. Animals were weighed and blood samples were taken on d 0, 7, and 14 of the study, and LCFA were analyzed. The use of L-Flaxseed in study 3 increased plasma concentrations of ALA to more than 4 times the level observed in cattle fed unprotected flaxseed, suggesting the dolomitic lime hydrate was effective as a protective barrier against biohydrogenation.