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