Dietary fatty acids and lipoproteins on progression of age-related macular degeneration

Age-related macular degeneration (AMD) is a medical condition of central loss vision and blindness. Numerous studies have revealed that changes on certain dietary fatty acids (FAs) could have useful for AMD management. This review summarizes the effects of dietary omega-3 long-chain PUFAs, MUFAs, and SFAs, and lipoproteins on AMD. Findings are consistent with the beneficial role of dietary omega-3 long-chain PUFAs, while the effects of dietary MUFAs and SFAs appeared to be ambiguous with respect to the possible protection from MUFAs and to the possible adverse impact from SFAs on AMD. Some of the pathological mechanisms associated with lipoproteins on AMD share those observed previously in cardiovascular diseases. It was also noticed that the effects of FAs in the diet and lipoprotein on AMD could be modulated by genetic variants. From a population health perspective, the findings of this review are in favour of omega-3 long-chain FAs recommendations in a preventive and therapeutic regimen to attain lower AMD occurrence and progression rates. Additional long-term and short-term nutrigenomic studies are required to clearly establish the role and the relevance of interaction of dietary FAs, lipoproteins, and genes in the genesis and progression of AMD

An opinion on the regulation of bone marrow adipose tissue by dietary fatty acids

Obesity has a significant impact on predisposition to various diseases and also affects the viabil­ity and choice of haematopoietic stem cells (HSCs) to favour myeloid cell production and/or turnover, all of which are extremely important for the functioning of immune system. As the production of blood cells and mobilization of HSCs and their progeny are regulated, at least in part, by multifaceted interactions through signals that come from the bone marrow (BM) microenvironment, it does not seem astonishing to assume that circumstances that cause alterations in BM structure will unavoidably cause alterations in mesenchymal cells such as adipocytes and lineages from HSCs. The existence of adipose tissue in BM or marrow fat (BMAT) is well known, although its origin, expansion, and functions are poorly understood. Inspired by other studies showing the potential role for olive oil and omega-3 long chain polyunsaturated fatty acids (omega-3 PUFAs) on BM health, and by our own preliminary findings showing the effects of monounsaturated (olive oil) but not saturated (milk cream) dietary fats to contain neutrophils and CD14high monocytes in BM during postprandial periods in healthy volunteers, herein we asked whether dietary fats (saturated fatty acids, SFAs, monounsatu­rated fatty acids, MUFAs, and omega-3 PUFAs) may be a candidate lifestyle factor to modulate the expansion, composition, and function of BMAT, the infiltration of adipose tissue macrophages (ATMs) in BMAT and the mobilization of HSCs and mature myeloid cells from BM during high-fat-induced obesity in mice. This is the first time that the interplay between different dietary fatty acids, obesity, and BM is addressed.Spanish Ministry of Science, Innovation and Universities AGL2016-80852-

A microRNA expression signature of the postprandial state in response to a high-saturated-fat challenge

The postprandial hypertriglyceridemia is an important and largely silent disturbance involved in the genesis of numerous pathological conditions. Exaggerated and prolonged states of postprandial hypertriglyceridemia are frequently related to the ingestion of meals enriched in saturated fatty acids (SFAs). MicroRNAs are noncoding RNAs that function as gene regulators and play significant roles in both health and disease. However, differential miRNA expression between fasting and postprandial states has never been elucidated. Here, we studied the impact of a high-saturated-fat meal, mainly rich in palmitic acid, on the miRNA signature in peripheral blood mononuclear cells (PBMCs) of nine male healthy individuals in the postprandial period by using a two-step analysis: miRNA array and validation through quantitative real-time polymerase chain reaction. Compared with miRNA expression signature in PBMCs at fasting, 36 miRNAs were down-regulated and 43 miRNAs were up-regulated in PBMCs at postprandial hypertriglyceridemic peak. Six chromosomes (3, 7, 8, 12, 14 and 19) had nearly half (48.1%) of dysregulated miRNA-gene-containing regions. Down-regulated miR-300 and miR-369-3p and up-regulated miR-495-3p, miR-129-5p and miR-7-2-3p had the highest number of target genes. The differentially expressed miRNAs and their predicted target genes involved pathways in cancer, MAPK signaling pathway, endocytosis and axon guidance. Only down-regulated miRNAs notably targeted PI3K-Akt signaling pathways, whereas only up-regulated miRNAs targeted focal adhesion, Wnt signaling pathway, transcriptional misregulation in cancer and ubiquitin-mediated proteolysis. This is the first study of miRNA expression analysis of human PBMCs during postprandial hypertriglyceridemia and offers insight into new potential mechanisms by which dietary SFAs influence health or disease.Ministerio de Economía y Competitividad AGL2011-29008, AGL2016-80852-

Unsaponifiable fraction isolated from grape (vitis vinifera l.) seed oil attenuates oxidative and inflammatory responses in human primary monocytes

Grape (Vitis vinifera L.) seed has well-known potential for production of oil as a byproduct of winemaking and is a rich source of bioactive compounds. Herein, we report that the unsaponifiable fraction (UF) isolated from grape seed oil (GSO) possesses anti-oxidative and anti-inflammatory properties towards human primary monocytes. The UF isolated from GSO was phytochemically characterized by GC-MS and HPLC. Freshly obtained human monocytes were used to analyse the effects of GSOUF (10–100 μg mL−1) on oxidative and inflammatory responses using FACS analysis, RT-qPCR, and ELISA procedures. GSOUF skewed the monocyte plasticity towards the anti-inflammatory non-classical CD14+CD16++ monocytes and reduced the inflammatory competence of LPS-treated human primary monocytes diminishing TNF-α, IL-1β, and IL-6 gene expression and secretion. In addition, GSOUF showed a strong reactive oxygen species (ROS)-scavenging activity, reducing significantly nitrite levels with a significant decrease in Nos2 gene expression. Our results suggest that the UF isolated from GSO has significant potential for the management of inflammatory and oxidative conditions and offer novel benefits derived from the consumption of GSO in the prevention of inflammation-related diseases

Pharmacological effects of mitraphylline from Uncaria tomentosa in primary human monocytes: Skew toward M2 macrophages

Ethnopharmacological relevance Uncaria tomentosa (Willdenow ex Roemer & Schultes) DC. (Rubiaceae) is a Peruvian thorny liana, commonly known as "cat's claw", and traditionally used in folk medicine to deal with several inflammatory diseases. Mitraphylline (MTP) is the most abundant pentacyclic oxindolic alkaloid (POA) from U. Tomentosa and has been reported to modify the inflammatory response. Herein, we have sought to identify the mechanisms underlying this modulatory effect of MTP on primary human monocytes and its ability to regulate differentiation processes on human primary monocyte and monocyte-derived macrophages. Material and methods In vitro studies with human primary monocytes and monocyte-derived macrophages were performed. Monocytes and M0 macrophages were exposed to MTP (25 μM) and LPS (100 ng/mL). M0 macrophages were polarized to M1 and M2 phenotypes in the absence or presence of MTP. The activation state of monocytes/macrophages was assessed by flow cytometry, gene expression and protein analysis of different specific markers. Results In human primary monocytes, the incubation of MTP for 24 h reduced the number of classical (CD14++CD16-) and intermediate (CD14++CD16+) subsets when compared to untreated or LPS-treated cells. MTP also reduced the chemotactic capacity of human primary monocytes. In addition, MTP promoted the polarization of M0 macrophages toward an anti-inflammatory M2 phenotype, the abrogation of the release of pro-inflammatory cytokines such as TNFα, IL-6 or IL-1β, as well as the restoration of markers for M2 macrophages in LPS-treated M1 macrophages. Conclusions Our results suggest that MTP may be a key modulator for regulating the plasticity of monocytes/macrophages and the attenuation of the inflammatory response

The effects of exogenous fatty acids and niacin on human monocyte-macrophage plasticity

Scope: Macrophage plasticity allows adapting to different environments, having a dual activity in inflammatory-related diseases. Our hypothesis is that the type of dietary fatty acids into human postprandial triglyceride-rich lipoproteins (TRLs), alone or in combination with niacin (vitamin B3), could modulate the plasticity of monocytes-macrophages. Methods and results: We isolated TRLs at the postprandial peak from blood samples of healthy volunteers after the ingestion of a meal rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated fatty acids (LCPUFAs). Autologous monocytes isolated at fasting were first induced to differentiate into naïve macrophages. We observed that postprandial TRL-MUFAs, particularly in combination with niacin, enhance competence to monocytes to differentiate and polarise into M2 macrophages. Postprandial TRL-SFAs made polarised macrophages prone to an M1 phenotype. In contrast to dietary SFAs, dietary MUFAs in the meals plus immediate-release niacin primed circulating monocytes for a reduced postprandial pro-inflammatory profile. Conclusion: Our study underlines a role of postprandial TRLs as a metabolic entity in regulating the plasticity of the monocyte-macrophage lineage and also brings an understanding of the mechanisms by which dietary fatty acids are environmental factors fostering the innate immune responsiveness in humans.Ministerio de Ciencia e Innovación AGL2011- 2900

Minor compounds from virgin olive oil attenuate LPS-induced inflammation via visfatin-related gene modulation on primary human monocytes

We have analyzed the effects of minor compounds found in the unsaponifiable fraction (UF) and in the phenolic fraction (PF) of virgin olive oil (VOO) on LPS-induced inflammatory response via visfatin modulation in human monocytes. For this purpose, monocytes were incubated with UF and PF at different concentrations and the pro-inflammatory stimulus LPS for 24 hr; squalene (SQ) and hydroxytyrosol (HTyr), the main components in UF and PF, respectively, were also used. The relative expression of both pro-inflammatory and anti-inflammatory genes, as well as other genes related to the NAD+-biosynthetic pathway was evaluated by RT-qPCR; and the secretion of some of these markers was assessed by ELISA procedures. We found that UF, SQ, PF, and HTyr prevented from LPS-induced dysfunctional gene expression and secretion via visfatin-related gene modulation in human monocytes. These findings unveil a potential beneficial role for minor compounds of VOO in the prevention of inflammatory-disorders. Practical application: In this project, potential health benefits of VOO micronutrients (unsaponifiable and phenolic compounds) were confirmed through anti-inflammatory assays. Our results reveal new interesting researching goals concerning nutrition by considering the role of bioactive VOO compounds in the prevention and progress of diseases related to inflammation

Distribution of erythrocyte membrane cholesterol in human essential hypertension

[Objective]: To determine whether the cholesterol distribution is impaired in erythrocyte membranes of normo- and hypercholesterolaemic patients with untreated essential hypertension. [Design]: Observational case-control study. [Methods]: Erythrocytes were prepared from venous blood samples obtained from normotensive subjects and hypertensive patients. The membrane cholesterol distribution was measured by cholesterol oxidation to cholestenone after continuous cholesterol oxidase treatment. The membrane cholesterol content was determined. The ability of cells to be labelled with [3H]-cholesterol was also tested. [Results]: The cholesterol distribution was asymmetric in erythrocyte membranes of the control subjects and hypertensive patients. The oxidation rate was faster in normotensive subjects, and no differences were found between normo- and hypercholesterolaemic hypertensive patients. Total cholesterol mass was lower in erythrocyte membranes of hypertensive patients, as indicated by a higher incorporation of radioactive cholesterol. [Conclusion]: These data suggest that the membrane cholesterol distribution is impaired in patients with untreated essential hypertension, and support the presence of cholesterol-rich domains in the erythrocyte membrane inner monolayer

Composición emulsionada de grasa saturada en agua, su preparación y utilización para la evaluación de la tolerancia a los triglicéridos

La presente invención se refiere a una composición líquida emulsionada que presenta un comportamiento monomodal estable en el tiempo y que está compuesta por agua, un hidrato de carbono, una grasa saturada, un emulgente y un saborizante. Otro aspecto de la invención se refiere al procedimiento de obtención de la composición emulsionada que incluye un doble tratamiento homogeneizador. Finalmente, la invención se refiere al uso de la composición emulsionada para evaluar la tolerancia a los triglicéridos en humanos, a través de un procedimiento estandarizado que comprende la administración oral de una cantidad calculada en función de la superficie corporal de las personas que han de ingerirlo, y la determinación del pico de triglicéridos en sangre y del tiempo de aclaramiento de los mismos, en un reducido periodo de tiempo.Peer reviewedConsejo Superior de Investigaciones Científicas, Universidad de SevillaB1 Patente sin examen previ

Opinión del Comité Científico de la Agencia Española de Seguridad Alimentaria y Nutrición (AESAN) relativa a la propuesta de la Comisión Europea (CE) sobre alegaciones nutricionales de ácidos grasos monoinsaturados (AGM) en alimentos y consideraciones sobre la misma aportadas por la Autoridad Europea de Seguridad Alimentaria

[EN]: In the context of the Proposal of Regulation concerning the use of nutrition and health claims in the labelling, presentation and advertising of foods, the European Food Safety Authority (EFSA) has issued a Scientific Opinion on possible nutrition claims related to omega-3 fatty acids, monounsaturated fat, unsaturated fat and polyunsaturated fat. This Opinion is an initial response to a question raised by the European Commission in the following terms: “The European Commission requests the EFSA to issue an opinion on the scientific substantiation of the nutrition claims relating to omega-3 fatty acids, monounsaturated fat, polyunsaturated fat and unsaturated fat.” In this context the Authority is asked to review the scientific merits of the following proposed claims and advise on their addition to the Annex of the proposed Regulation: High monounsaturated fat: A claim that a food is high in monounsaturated fat, and any claim likely to have the same meaning for the consumer, may only be made where at least 45% of the fatty acids present in the product derive from monounsaturated fat under the condition that saturated fat must not provide more than 10% of energy”. The criteria proposed by the European Commission for monounsaturated fat claim (SFA<10%) is contradictory to the recommendation expressed by their own EFSA Scientific Panel in its report, in the same way that it contradicts what has been endorsed by several national and international organizations. The Scientific Panel of EFSA considers to be an anomaly the fact that, while olive oil is a good monounsaturated fatty acids source, it cannot qualify for the “high monounsaturated fat” claim, when failing to fulfil the additional condition of which the saturated fatty acids content in the product must be less than 10% of the energy. After considering scientific aspects of greatest interest related to the matter, the Scientific Committee of the AESAN concludes that the criteria proposed by the European Commission erroneously considers olive oil to be excluded from the possibility of showing the claim “high monounsaturated fat” based just on the condition that saturated fat must not provide more than 10% of energy. Numerous independent scientific opinions, including that of EFSA, demonstrate that beneficial effects have been observed when increasing the relationship between the content of monounsaturated fatty acids and saturated fatty acids, a circumstance that occurs in olive oil (main monounsaturated fatty acids source of the Mediterranean diet), a product whose consumption is recommended at an international level.[ES]: En el contexto de lo previsto en la propuesta de Reglamento sobre el uso de alegaciones nutricionales y de salud en el etiquetado, presentación y publicidad de los alimentos, la Autoridad Europea de Seguridad Alimentaria (EFSA) ha emitido una Opinión científica sobre posibles alegaciones nutricionales relativas a ácidos grasos omega-3, grasa monoinsaturada, insaturada y poliinsaturada. Esta Opinión constituyó una primera respuesta a una cuestión que le fue planteada por la Comisión Europea en los siguientes términos: "La Comisión Europea requiere a la EFSA que emita una Opinión sobre la substanciación científica de las alegaciones nutricionales relativas a ácidos grasos omega-3, grasa monoinsaturada, poliinsaturada e insaturada”. En este contexto se plantea a la EFSA que revise los méritos científicos de las siguiente alegación propuesta y que asesore sobre su adición al Anexo de la Propuesta de Reglamento: "Alto contenido en ácidos grasos monoinsaturados: solamente podrá alegarse que un alimento posee un alto contenido en ácidos grasos monoinsaturados o cualquier declaración que tenga el mismo significado para el consumidor, si al menos un 45% de los ácidos grasos que contiene el producto es grasa monoinsaturada bajo la condición de que el contenido en grasa saturada no debe proporcionar más del 10% de la energía". El criterio propuesto por la Comisión Europea para las alegaciones de ácidos grasos monoinsaturados (AGS<10%) resulta contradictorio con la recomendación expresada por el propio panel científico de la EFSA en su informe, del mismo modo que contradice lo avalado por diversas organizaciones nacionales e internacionales. El Panel Científico de la EFSA considera una anomalía el hecho de que, siendo el aceite de oliva una buena fuente de ácidos grasos monoinsaturados, no pueda ser incluido en el grupo de alimentos con alto contenido en ácidos grasos monoinsaturados, al incumplir la condición adicional de que el contenido de ácidos grasos saturados en el producto debe ser inferior al 10% de la energía. El Comité Científico de la Agencia Española de Seguridad Alimentaria y Nutrición tras haber considerado los aspectos científicos de mayor interés relacionados con la cuestión concluye, entre otras cuestiones, que considera erróneo el criterio propuesto por la Comisión Europea para excluir al aceite de oliva de la posibilidad de ostentar la alegación “alto contenido en ácidos grasos monoinsaturados” basado únicamente en que el contenido de ácidos grasos saturados debe ser inferior al 10% de su energía. Numerosas opiniones científicas independientes, incluida la de la EFSA demuestran los efectos beneficios que se han observado al incrementar la relación entre el contenido de ácidos grasos monoinsaturados y ácidos grasos saturados, circunstancia que se da en el aceite de oliva (principal fuente de ácidos grasos monoinsaturados de la dieta mediterránea) producto de consumo recomendado a nivel internacional.Peer reviewe