Effect of food extracts and bioactive food compounds on the mechanism of atherosclerosis and nutritional biomarkers

Primera, estudiar los efectos de un extracto de cacahuete rico en polifenoles y de compuestos bioactivos (alfa-tocoferol) en modelos celulares a nivel de inflamación (células monocíticas THP-1) y disfunción endotelial (células endoteliales de aorta humana; HAEC), respectivamente. Segunda, optimizar el volumen sanguíneo caracterizando el perfil de metabolitos acuosos y lipídicos, la composición de ácidos grasos, la detección de subclases de lipoproteínas y de polifenoles en plasma y glóbulos rojos. El extracto de cacahuete ejerce efectos anti-inflamatorios mediante la inhibición de la proteína del TNF-α extracelular, a través de la inhibición de la activación del factor de transcripción c-Jun. El alfa-tocoferol mejora la función endotelial mediante la inhibición de la VCAM-1 y en menor grado sobre la E-selectina e ICAM-1. El plasma y glóbulos rojos aportan información metabolómica complementaria y se elegirá uno u otro en función del objetivo de los estudios en humanos.The thesis addresses two major issues. Firstly: The study the effects of polyphenol-rich peanut extract and bioactive compounds (alpha-tocopherol) in cellular models of inflammation (monocytic cells; THP-1) and on endothelial dysfunction (human aortic endothelial cells; HAEC), respectively. Secondly: The optimisation of blood sampling for human studies to characterise the profile of aqueous and lipid metabolites, fatty acid composition, lipoprotein subclasses, and polyphenol content of plasma and red blood cells. Peanut extract exerts anti-inflammatory effects by inhibiting extracellular TNF-α protein via the inhibition of c-Jun transcription factor activation. Alpha-tocopherol improves endothelial function by inhibiting VCAM-1 and, to a lesser extent, E-selectin and ICAM-1. Analyses of metabolites in plasma and red blood cells generate complementary information. The measurements may need to be performed in either, or both, matrices, depending on the objectives of the study

In vitro metabolomic approaches to investigating the potential biological effects of phenolic compounds: an update

Dietary phenolic compounds (PCs) have been receiving interest for their presumed roles in disease prevention. However, there is a lack of studies on the underlying molecular mechanisms. In this regard, in vitro metabolomic approaches are suitable for the investigation of the molecular changes in response to PC exposure. Up to date, the biological effects of PCs have only been examined for PCs from rosemary (Rosmarinus officinalis), olive oil, and resveratrol using cell-based metabolomic approach, although transcriptomic and/or proteomic studies have also been conducted in the same in vitro cell experiment in some cases. Our integral analysis of the reviewed studies suggest that PCs may be involved not only in basic cellular processes or macro- and micro-nutrient metabolism, but also in specific metabolic pathways that have been thoroughly investigated. These modulated pathways could have a clinical impact on neurodegenerative diseases, type 2 diabetes, cancer, and cardiovascular diseases. In conclusion, the in vitro metabolomic approaches provide additional information of the molecular mechanisms involved in disease risk reduction of dietary PCs. In order to elucidate the mechanisms of action of PCs, more metabolomic cell-based studies are needed and testing the physiological conjugated forms of PCs in these cell systems could be of special interest.This work was partially supported by grants (Grant Nos. AGL2009-13517-C03-03 and AGL2012-40144-C03-02) from the Spanish Ministry of Education and Science (Ministerio de Educación y Ciencia, Spain), a Sara Borrell post-doctoral grant (CD14/00275; Spain), a Pla estratègic de recerca i innovació en salut (PERIS) post-doctoral grant (SLT002/16/00239; Catalunya, Spain). We also thank the support of Institut d’Investigació Sanitària Pere Virgili (IISPV) and Centre Tecnològic de Nutrició i Salut (CTNS), Reus, Spain. NFOC-Salut group is a consolidated research group of Generalitat de Catalunya, Spain (2014 SGR 873

Determinants of HDL Cholesterol Efflux Capacity after Virgin Olive Oil Ingestion: Interrelationships with Fluidity of HDL Monolayer

Scope: Cholesterol efflux capacity of HDL (CEC) is inversely associated with cardiovascular risk. HDL composition, fluidity, oxidation, and size are related with CEC. We aimed to assess which HDL parameters were CEC determinants after virgin olive oil (VOO) ingestion. Methods and results: Post‐hoc analyses from the VOHF study, a crossover intervention with three types of VOO. We assessed the relationship of 3‐week changes in HDL‐related variables after intervention periods with independence of the type of VOO. After univariate analyses, mixed linear models were fitted with variables related with CEC and fluidity. Fluidity and Apolipoprotein (Apo)A‐I content in HDL was directly associated, and HDL oxidative status inversely, with CEC. A reduction in free cholesterol, an increase in triglycerides in HDL, and a decrease in small HDL particle number or an increase in HDL mean size, were associated to HDL fluidity. Conclusions: HDL fluidity, ApoA‐I concentration, and oxidative status are major determinants for CEC after VOO. The impact on CEC of changes in free cholesterol and triglycerides in HDL, and those of small HDL or HDL mean size, could be mechanistically linked through HDL fluidity. Our work points out novel therapeutic targets to improve HDL functionality in humans through nutritional or pharmacological interventions.Fil: Fernández Castillejo, Sara. Universitat Rovira I Virgili; EspañaFil: Rubió, Laura. Universitat Rovira I Virgili; España. Universidad de Lleida; EspañaFil: Hernáez, Álvaro. Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición; EspañaFil: Catalán, Úrsula. Universitat Rovira I Virgili; EspañaFil: Pedret, Anna. Universitat Rovira I Virgili; EspañaFil: Valls, Rosa M.. Universitat Rovira I Virgili; EspañaFil: Mosse, Juana Inés. Universidad de Lleida; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Covas, Maria Isabel. Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición; EspañaFil: Remaley, Alan T.. National Institutes of Health; Estados UnidosFil: Castañer, Olga. Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición; EspañaFil: Motilva, Maria José. Universidad de Lleida; EspañaFil: Solá, Rosa. Universitat Rovira I Virgili; Españ

Phosphoproteomic analysis and protein-protein interaction of rat aorta GJA1 and rat heart FKBP1A after secoiridoids consumption from virgin olive oil: A functional proteomics approach

Protein functional interactions could explain the biological response of secoiridoids (SECs), main phenolic compounds in virgin olive oil (VOO). The aim was to assess protein¿protein interactions (PPIs) of the aorta gap junction alpha-1 (GJA1) and the heart peptidyl-prolyl cis-trans isomerase (FKBP1A), plus the phosphorylated heart proteome, to describe new molecular pathways in the cardiovascular system in rats using nanoliquid chromatography coupled with mass spectrometry. PPIs modified by SECs and associated with GJA1 in aorta rat tissue were calpain, TUBA1A, and HSPB1. Those associated with FKBP1A in rat heart tissue included SUCLG1, HSPE1, and TNNI3. In the heart, SECs modulated the phosphoproteome through the main canonical pathways PI3K/mTOR signaling (AKT1S1 and GAB2) and gap junction signaling (GAB2 and GJA1). PPIs associated with GJA1 and with FKBP1A, the phosphorylation of GAB2, and the dephosphorylation of GJA1 and AKT1S1 in rat tissues are promising protein targets promoting cardiovascular protection to explain the health benefits of VOO.The work summarized in this paper was supported in part by grants (grant nos. MEFOPC Project, AGL2012-40144-C03-02 and AGL2012-40144-C03-03, and AppleCOR Project, AGL2016-76943-C2-2-R) from the Ministerio de Economía, Industria y Competitividad, the Agencia Estatal de Investigación (AEI), and the European Regional Development Fund (ERDF). L.R. is supported by a Sara Borrell postdoctoral grant (CD14/00275; Spain), A.P. is supported by a postdoctoral grant (PTQ-15-08068; Spain), and Ú.C. is supported by a Pla Estratègic de Recerca i Innovació en Salut (PERIS) postdoctoral grant (SLT002/16/00239; Catalunya, Spain)