Lídia Cedó and Escola-Gil
It is well known that olive oil consumption has beneficial effects on cardiovascular disease prevention. Such benefits can be attributed, at least in part, to the olive oil phenolic compounds, which possess antioxidant and anti-inflammatory properties. In 2011, the European Food Safety Authority claimed that in order to protect lipids from oxidative damage, the consumption of hydroxytyrosol and its derivatives in olive oil should be of 5 mg/day. However, the phenolic compounds concentration in many commercial virgin olive oils is too low to reach the recommended daily dose. Therefore, olive oil enriched with its own phenolic compounds could be of interest to increase the dose of these beneficial compounds without increasing the fat intake. In this context, a randomized, controlled trial was designed to investigate the effects of virgin olive oil enriched with phenolic compounds on high-density lipoprotein (HDL) quantity and quality in hypercholesterolemic subjects (Virgin Olive Oil and HDL Functionality: VOHF project) . The main results of VOHF project concluded that virgin olive oil enriched with phenolic compounds promoted cardioprotective changes in humans, by modulating HDL proteome, increasing fat-soluble antioxidants, improving HDL subclasses distribution, reducing the lipoprotein insulin resistance index, increasing endogenous antioxidant enzymes, protecting DNA from oxidation, ameliorating endothelial function, and increasing fecal microbial metabolic activity .
The main cardioprotective function of HDL is related with its ability to facility removal of cholesterol from macrophage foam cells located in the artery wall, followed by the transfer of cholesterol to the liver, and ultimately, to the gut for excretion in the feces . This key cardioprotective pathway is known as the macrophage-specific reverse cholesterol transport and this is considered the major route for elimination of relevant cholesterol from the body. A key methodological problem for quantifying reverse cholesterol transport from macrophages is that the macrophage cholesterol pool is a minor contributor to the total reverse cholesterol transport from peripheral cells. To overcome this quantitative problem, our group developed an assay for measuring in vivo macrophage-to-feces reverse cholesterol transport by tracing the reverse radiolabelled cholesterol transport from lipid-laden macrophages to feces . Therefore, although this technique cannot be performed currently in humans, it has been extensively studied in mice with the ultimate aim of translating the knowledge to humans.
In this way, our last work, published in Biomedicines , analysed the effects of phenolic compounds-enriched virgin olive oil on reverse cholesterol transport from macrophages to feces. In this study, entitled “Phenol-enriched virgin olive oil promotes macrophage-specific reverse cholesterol transport in vivo”, mice were given the same virgin olive oil enriched with its own phenolic compounds used in the VOHF project. One group of mice was administered saline as a control, and two additional groups of mice were administered a refined olive oil or the phenolic extract used to prepare the enriched virgin olive oil, in order to discern whether the effects of the enriched virgin olive oil were mainly due to the olive oil fat or the phenolic compounds. What we found is that both enriched virgin olive oil and the phenolic extract increased serum HDL cholesterol and its ability to remove cholesterol from macrophages. More importantly, these results were concomitant with an enhanced ability of HDL to promote the transport of cholesterol from macrophages to feces in vivo. In the same study, phenolic extract was also found to upregulate the expression of the main macrophage transporter involved in cholesterol efflux to HDL, the ATP binding cassette A1 (ABCA1). Therefore, the promotion of the reverse cholesterol transport by the olive oil phenolic compound was closely related to their ability to induce macrophage expressionof the gene Abca1, thereby increasing their potential to facilitate HDL-mediated removal of cholesterol (see image).
In conclusion, the results from this study, together with the previous results from the VOHF project, would indicate that virgin olive oil enriched with its own phenolic compounds could be considered as functional food with significant cardioprotective properties.
Dr. Lídia Cedó obtained a BS in Biochemistry and a MS in Nutrition and Metabolism from Universitat Rovira i Virgili of Tarragona. In 2013 she got her doctorate in the same university, focused on the effects of grape seed procyanidins on proliferation and apoptosis of pancreatic cells, under the supervision of Dr. Montserrat Pinent. Since 2013 she worked as a postdoc in the group Bases Metabòliques del Risc Cardiovascular, led by Dr. Francisco Blanco, from the Institut d’Investigacions Biomèdiques Sant Pau in Barcelona. Her main line of research focused on the development and metabolic characterization of genetically modified mice as models of dyslipemia (and more specifically in HDL alterations), obesity, diabetes, and arteriosclerosis, and in applied studies of nutritional interventions and pharmacological treatments. Outside the lab, Lídia enjoys sharing her life with her husband and two-years-old daughter, she loves reading, photography, and spending time with family and friends.
Dr. Escola-Gil started his research activity as senior researcher at the Research Institute of the Hospital of Santa Cruz and San Pablo in 2003. He also works as Associate Professor in the Department of Biochemistry and Molecular Biology of the Faculty of Medicine of the Universitat Autònoma de Barcelona. He has received overlapping funding as Principal Investigator for projects of the Instituto de Salud Carlos III, including his participation in the CIBER of diabetes and associated metabolic diseases as coPI (CIBERDEM) and in a COST action of the European Union on HDL (BM0904). His main line of research focuses on the development and metabolic characterization of experimental models of dyslipidemia (particularly in HDL-related alterations), obesity, diabetes and arteriosclerosis. In recent years, he has expanded this line of research with applied studies of nutritional interventions and pharmacological therapies targeting HDL atheroprotective functions in patients affected by chronic cardiometabolic diseases and diseases with a high cardiovascular risk as well as in patients with breast or thyroid cancer. On the other hand, he also participates in projects focused on Molecular (biochemical and genetic levels) diagnosis and characterization of inherited dyslipidemias (such as familial hypoalphalipoproteinemia, familial hyperchylomicronemia, familial dysbetalipoproteinemia, familial hypobetalipoproteinemia, abetalipoproteinemia, familial combined hyperlipemia and familial hypercholesterolemia). He has published over 100 international research papers and supervised 6 PhD students and over 20 master students.
- Pedret, A.; Fernández-Castillejo, S.; Valls, R.-M.; Catalán, Ú.; Rubió, L.; Romeu, M.; Macià, A.; López de Las Hazas, M.C.; Farràs, M.; Giralt, M.; et al. Cardiovascular Benefits of Phenol-Enriched Virgin Olive Oils: New Insights from the Virgin Olive Oil and HDL Functionality (VOHF) Study. Mol. Nutr. Food Res. 2018, 62, e1800456.
- Lee-Rueckert M; Escola-Gil J.C.; Kovanen, P.T. HDL functionality in reverse cholesterol transport — Challenges in translating data emerging from mouse models to human disease. Biochimica et Biophysica Acta (BBA) – Molecular and Cell Biology of Lipids, 2016, volume 1861, Issue 7, Pages 566-583
- Cedó, L.; Fernández-Castillejo, S.; Rubió, L.; Metso, J.; Santos, D.; Muñoz-Aguayo, D.; Rivas-Urbina, A.; Tondo, M.; Méndez-Lara, K.A.; Farràs, M.; Jauhiainen, M.; Motilva, M.-J.; Fitó, M.; Blanco-Vaca, F.; Solà, R.; Escolà-Gil, J.C. Phenol-Enriched Virgin Olive Oil Promotes Macrophage-Specific Reverse Cholesterol Transport In Vivo. Biomedicines 2020, 8, 266.