Nutrigenomics and Atherosclerosis: The Postprandial and Long-Term Effects of Virgin Olive Oil Ingestion

Metals technology / metallurg

Fatty Acids on Osteoclastogenesis

Excessive bone resorption is a hallmark on the onset and development of bone diseases, including osteoporosis, periodontitis, and rheumatoid arthritis. Osteoclasts are bone‐resorbing multinucleated cells that differentiate from hematopoietic progenitors of the myeloid lineage. The regulation of this differentiation process is considered an effective therapeutic intervention to the treatment of pathological bone loss. Dietary fatty acids (FAs), transported in the form of postprandial triglyceride‐rich lipoproteins, have been linked with inflammation and oxidative stress associated to the overactivation of circulating leukocytes. Monocyte differentiation by soluble cytokines is known to up‐regulate osteoclast maturation via increased expression levels of receptor activator for nuclear factor‐κB ligand relative to osteoprotegerin. This review summarizes the effects of dietary omega‐3 long‐chain polyunsaturated fatty acids, monounsaturated fatty acids, and saturated fatty acids on plasticity during osteoclast formation and function

Chapter Beyond Dietary Fatty Acids as Energy Source: A Point of View for the Prevention and Management of Type 2 Diabetes

Medical genetic

Effects of minor compounds from virgin olive oil on inflammatory response in human leukocytes

Mediterranean diet protects against cardiovascular diseases such as atherosclerosis, now considered an inflammatory disorder. Virgin olive oil is one of the most important foods in this diet, leading to the suggestion that health benefits of Mediterranean diet are achieved at least partially due to the consumption of virgin olive oil. Extra virgin olive oil (EVOO) is the highest quality oil based on its chemical and sensorial properties. Our aim was to evaluate the anti-inflammatory effects of minor compounds found in the unsaponifibale fraction of EVOO on activated human monocytes and neutrophils. For this purpose, we isolated monocytes and neutrophils from blood samples of healthy volunteers. We also isolated the unsaponifiable fraction (UF) from EVOO. Cells were incubated with UF at different concentrations and the pro-inflammatory stimulus LPS. Afterwards, RNA was obtained from cells and then converted into cDNA. The relative gene expression of pro-inflammatory and anti-inflammatory markers was assessed by qRT-PCR. We found that UF from EVOO reduced relative gene expression of pro-inflammatory markers in a dose-dependent manner both in human monocytes and neutrophils. In contrast, UF from EVOO increased relative gene expression of anti-inflammatory markers in these cells. These findings unveil a role of UF from EVOO in the benefits from consumption of EVOO in disorders related to inflammation

Membrane composition and dynamics: A target of bioactive virgin olive oil constituents

AbstractThe endogenous synthesis of lipids, which requires suitable dietary raw materials, is critical for the formation of membrane bilayers. In eukaryotic cells, phospholipids are the predominant membrane lipids and consist of hydrophobic acyl chains attached to a hydrophilic head group. The relative balance between saturated, monounsaturated, and polyunsaturated acyl chains is required for the organization and normal function of membranes. Virgin olive oil is the richest natural dietary source of the monounsaturated lipid oleic acid and is one of the key components of the healthy Mediterranean diet. Virgin olive oil also contains a unique constellation of many other lipophilic and amphipathic constituents whose health benefits are still being discovered. The focus of this review is the latest evidence regarding the impact of oleic acid and the minor constituents of virgin olive oil on the arrangement and behavior of lipid bilayers. We highlight the relevance of these interactions to the potential use of virgin olive oil in preserving the functional properties of membranes to maintain health and in modulating membrane functions that can be altered in several pathologies. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy

Functional and structural analysis of five mutations identified in methylmalonic aciduria cbIB type

ATP:cob(I)alamin adenosyltransferase (ATR, E.C.2.5.1.17) converts reduced cob(I)alamin to the adenosylcobalamin cofactor. Mutations in the MMAB gene encoding ATR are responsible for the cblB type methylmalonic aciduria. Here we report the functional analysis of five cblB mutations to determine the underlying molecular basis of the dysfunction. The transcriptional profile along with minigenes analysis revealed that c.584G>A, c.349-1G>C, and c.290G>A affect the splicing process. Wild-type ATR and the p.I96T (c.287T>C) and p.R191W (c.571C>T) mutant proteins were expressed in a prokaryote and a eukaryotic expression systems. The p.I96T protein was enzymatically active with a K M for ATP and K D for cob(I)alamin similar to wild-type enzyme, but exhibited a 40% reduction in specific activity. Both p.I96T and p.R191W mutant proteins are less stable than the wild-type protein, with increased stability when expressed under permissive folding conditions. Analysis of the oligomeric state of both mutants showed a structural defect for p.I96T and also a significant impact on the amount of recovered mutant protein that was more pronounced for p.R191W that, along with the structural analysis, suggest they might be misfolded. These results could serve as a basis for the implementation of pharmacological therapies aimed at increasing the residual activity of this type of mutations. Hum Mutat 31:1033–1042, 2010. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78057/1/21307_ftp.pd

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

Leukocyte Overexpression of Intracellular NAMPT Attenuates Atherosclerosis by Regulating PPAR gamma-Dependent Monocyte Differentiation and Function

Objective-Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) mediates inflammatory and potentially proatherogenic effects, whereas the role of intracellular NAMPT (iNAMPT), the rate limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD)(+) generation, in atherogenesis is largely unknown. Here we investigated the effects of iNAMPT overexpression in leukocytes on inflammation and atherosclerosis. Approach and Results-Low-density lipoprotein receptor-deficient mice with hematopoietic overexpression of human iNAMPT (iNAMPT(hi)), on a western type diet, showed attenuated plaque burden with features of lesion stabilization. This anti-atherogenic effect was caused by improved resistance of macrophages to apoptosis by attenuated chemokine (C-C motif) receptor 2-dependent monocyte chemotaxis and by skewing macrophage polarization toward an anti-inflammatory M2 phenotype. The iNAMPT(hi) phenotype was almost fully reversed by treatment with the NAMPT inhibitor FK866, indicating that iNAMPT catalytic activity is instrumental in the atheroprotection. Importantly, iNAMPT overexpression did not induce any increase in eNAMPT, and eNAMPT had no effect on chemokine (C-C motif) receptor 2 expression and promoted an inflammatory M1 phenotype in macrophages. The iNAMPT-mediated effects at least partly involved sirtuin 1-dependent molecular crosstalk of NAMPT and peroxisome proliferator-activated receptor.. Finally, iNAMPT and peroxisome proliferator-activated receptor. showed a strong correlation in human atherosclerotic, but not healthy arteries, hinting to a relevance of iNAMPT/peroxisome proliferator-activated receptor. pathway also in human carotid atherosclerosis. Conclusions-This study highlights the functional dichotomy of intracellular versus extracellular NAMPT, and unveils a critical role for the iNAMPT-peroxisome proliferator-activated receptor. axis in atherosclerosis

Growth differentiation factor 15 deficiency protects against atherosclerosis by attenuating CCR2-mediated macrophage chemotaxis

The TGF-β family member GDF-15 promotes lesion formation and plaque instability in atherosclerosis-prone LDLr-deficient mice