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

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

CD4+ and CD8+ T-cell responses in bone marrow to fatty acids in high-fat diets

Obesity is associated with disruptions in the adaptive immune system; however, dietary fatty acids in high-fat diets (HFDs) that induce obesity have consequences that are currently unclear regarding T-cell maintenance in bone marrow (BM). C57BL/6J mice were randomly assigned to isocaloric HFDs formulated with dietary fats rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), or MUFAs supplemented with eicosapentaenoic and docosahexaenoic acids for 20 weeks, followed by an analysis of the immunophenotypic feature of lymphocytes (CD3+) T and their subsets CD4+ and CD8+ T cells in spleen and BM, identification of fatty acids in BM extracellular fluid and analysis of the correspondence between fatty acids with the frequency of T-cell subsets in BM. Splenic CD3+ T cells were reduced irrespective of HFDs. In BM, CD3+ T cells were reduced after HFD-SFAs, while CD4+ T cells were increased after HFDs enriched in MUFAs and CD8+ T cells were reduced irrespective of HFDs. In BM extracellular fluid, the content of palmitic and myristic acids increased after HFD-SFAs and that of oleic acid increased after HFDs enriched in MUFAs. There was a statistical correspondence between HFD-induced changes in fatty acids in BM extracellular fluid and HFD-induced changes in the frequency of CD3+ and CD4+ T cells in BM. These findings reveal an undervalued critical role for dietary fatty acids in the selective acquisition of T-cell subsets in BM, highlighting that oleic acid existing in the surroundings of T-cell niches during HFD-induced obesity could be instrumental in the maintenance of CD4+ T cells.Fondo Social Europeo y Universidad de Sevilla-VPPI-USConsejo Superior de Investigaciones Científicas (CSIC)/Juan de la Cierva-FJCI-2017-3313

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-

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

Dietary fatty acids on aortic root calcification in mice with metabolic syndrome

Metabolic syndrome (MetS) is associated with obesity, dyslipidemia, type 2 diabetes, and chronic low-grade inflammation. The aim of this study was to determine the role of high-fat low-cholesterol diets (HFLCDs) rich in SFAs (HFLCD-SFAs), MUFAs (HFLCD-MUFAs) or MUFAs plus omega-3 long-chain PUFAs (HFLCD-PUFAs) on vascular calcification by the modulation of the RANKL/RANK/OPG system in the aortic roots of Lepob/obLDLR-/- mice. Animals fed with HFLCD-SFAs had increased weight and a greater atheroma plaque size, calcification, and RANKL/CATHK expression in the aortic root than mice on MUFA-enriched diets, with an increasing OPG expression in the aortic roots of the latter. Our study demonstrates that compared to dietary SFAs, MUFAs from olive oil protect against atherosclerosis by interfering with vascular calcification via the RANKL/RANK/OPG system in the setting of MetS. These findings open opportunities for developing novel nutritional strategies with olive oil as the most important dietary source of MUFAs (notably oleic acid) to prevent cardiovascular complications in MetS.Ministerio de Ciencia e Innovación AGL2011-2900