Mediterranean Diet Modulates Gene Expression of Cholesterol Efflux Receptors in High-Risk Cardiovascular Patients

Abstract

Dieta Mediterrània; Expressió Gènica; Receptors de Colesterol

Mediterranean Diet; Gene Expression; Cholesterol Receptors

Dieta Mediterránea; Expresión Génica; Receptores de Colesterol

In this study, we investigated gene expression related to cholesterol efflux receptors in individuals at high cardiovascular risk undergoing Mediterranean dietary interventions. Through transcriptomic analysis, we examined samples from two randomized controlled trials: PREDIMED and PREDIMED-Plus, with 151 and 89 elderly adults, respectively. Blood cells were isolated at baseline and after a 12-month intervention. In the PREDIMED trial, participants followed different Mediterranean diets: one supplemented with extra-virgin olive oil (traditional Mediterranean diet enriched with extra-virgin olive oil [MedDiet-EVOO]), another with nuts (MedDiet enriched with nuts MedDiet-Nuts [MedDiet-Nuts]), and a low-fat control diet. The PREDIMED-Plus trial compared an energy-reduced Mediterranean diet (Er-MedDiet) with physical activity to an ad libitum Mediterranean diet. Over time, mild but significant upregulation of genes like ATP binding cassette subfamily A member 1 (ABCA1), retinoid X receptor alpha (RXRA), retinoid X receptor beta (RXRB), and Nuclear Receptor Subfamily 1 Group H Member 3 (NR1H3) was observed in response to MedDiet-EVOO, MedDiet-Nuts, and Er-MedDiet. Notably, RXRA expression was higher in both MedDiet-EVOO and MedDiet-Nuts compared to the control diet. Differences in gene expression, particularly RXRA, ATP binding cassette subfamily G member 1 (ABCG1), NR1H3, and Peroxisome Proliferator Activated Receptor Delta (PPARD), were evident between MedDiet-Nuts and the control diet. In the PREDIMED-Plus trial, no significant differences in gene expression were found between dietary groups. Principal component analysis (PCA) and linear discriminant analysis (LDA) showed overlapping gene expression profiles across different Mediterranean diet interventions. In conclusion, our study highlights the cardiovascular health benefits of long-term adherence to a Mediterranean diet, both normocaloric and hypocaloric, primarily reflected by mild upregulation of cholesterol efflux-related genes-specifically involving RXRA, RXRB, ABCA1, ABCG1, Nuclear Receptor Subfamily 1 Group H Member 2(NR1H2), and PPARD-among elderly adults at high cardiovascular risk. This suggests a potential mechanism by which these diets may exert cardiovascular protective effects.

Diet, Mediterranean Gene Expression Regulation Cholesterol Efflux Cardiovascular Diseases Receptors, Lipoprotein

This work was framed within projects (PI18/00020; PI19/00017; PI16/00533; PI13/00233; PI20/00012; PI17/00214) funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union. This work was supported by grant CP21/00097 from Instituto de Salud Carlos III-Fondo Social Europeo Plus (FSE+); and by Agència de Gestió d'Ajuts Universitaris i de Recerca (2021 SGR 00144). This work was also supported by CB06/03/0028 from Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición. Amb el suport de la Fundació La Marató de TV3 (202312-30-31-32-33). The funders played no role in the study design, collection, analysis, or interpretation of data, and neither in the process of writing the manuscript and its publication. Javier Hernando-Redondo had received the Contrato Rio Hortega CM20/00085 grant.