Bioavailability and bioactivity of evoo (poly)phenol metabolites on cell metabolism and inflammation. Implications on metabolic syndrome complications

Mediterranean Diet is described as a favourable dietary regimen promoting health. Within its components, extra virgin olive oil (EVOO) has a high potential to positively impact hepatic metabolism with implications in health/disease. EVOO is a mixture of nutrients including fatty acids, plant sterols and other bioactive molecules like (poly)phenols. Using nutrigenomics in humans, UNIBA previously showed that an acute administration of Coratina EVOO [rich in (poly)phenols] has a positive impact on inflammatory cells transcriptome regulating inflammation, lipid/cholesterol metabolism, and cancer pathways (D’Amore et al BBA lipids 2016). These processes are crucial for the development of Metabolic Syndrome and its complications [e.g. Non-Alcoholic Steatohepatitis (NASH), cardio-metabolic disease and cancer]. This Project aims to dissect the role of EVOO components [fatty acids and (poly)phenol metabolites] in mediating EVOO effects, using integrative “omics” approaches in vitro.

UNIBA/UNIPR are carrying studies that will inform regarding changes in circulating lipidomics and (poly)phenol metabolites following EVOO intake. This information, together with a literature review, will point to 2-3 candidate molecules (because of strong modulation and/or potential biological effect) whose function will be tested in vitro on advanced culturing systems, including Organoids/Microtissues (e.g. human 3D liver cells co-cultured on Organs on Chip; Vacca et al Nature Metabolism 2020) also outsourcing some activities to the Roger Williams Institute of Hepatology London UK (international collaboration agreement with UNIBA). By mimicking in vitro healthy and pathological conditions (e.g. NASH, NASH-HCC) and by using state of the art “omics” approaches, this study will assess the bioactivity [changes in cells function (NGS) and lipidome (LC-MS)] and bioavailability [transformation of fatty acids and (poly)phenols by MS] of the compounds tested in health and disease.

This study has the potential to produce a large set of “omics” data that will help to profile the bioavailability and bioactivity of EVOO components in health and disease. This will help to understand the mechanism by which EVOO could exert its benefits on health, and to identify targets for pharmacological/nutraceutical approaches that are directly derived by EVOO and that could be used in clinic for prevention and treatment of metabolic disease. In specific, this study design will allow to dissect the mechanism of action of the most promising EVOO components on cell function with regards to 1) metabolism; 2) inflammatory pathways; 3) proliferation and cell death; 4) bioavailability and metabolism of (poly)phenols. This study will instruct if there is a specific bioactive molecule, among the metabolites of EVOO (poly)phenols, that can justify the health benefits of EVOO and that could be used to prevent the development and progression of Metabolic Syndrome and its complications.