Systematic bioinformatic analysis of nutrigenomic data of flavanols in cell models of cardiometabolic disease

Ruskovska, Tatjana and Massaro, Marika and Carluccio, Maria Annunziata and Arola-Arnal, Ana and Muguerza, Begoña and Vanden Berghe, Wim and Declerck, Ken and Bravo, Francisca Isabel and Calabriso, Nadia and Combet, Emilie and Gibney, Eileen R and Gomes, Andreia and Gonthier, Marie-Paule and Kistanova, Elena and Krga, Irena and Mena, Pedro and Morand, Christine and Nunes Dos Santos, Claudia and de Pascual-Teresa, Sonia and Rodriguez-Mateos, Ana and Scoditti, Egeria and Suárez, Manuel and Milenkovic, Dragan (2020) Systematic bioinformatic analysis of nutrigenomic data of flavanols in cell models of cardiometabolic disease. Food & Function, 11 (6). pp. 5040-5064.

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Flavanol intake positively influences several cardiometabolic risk factors in humans. However, the specific molecular mechanisms of action of flavanols, in terms of gene regulation, in the cell types relevant to cardiometabolic disease have never been systematically addressed. On this basis, we conducted a systematic literature review and a comprehensive bioinformatic analysis of genes whose expression is affected by flavanols in cells defining cardiometabolic health: hepatocytes, adipocytes, endothelial cells, smooth muscle cells and immune cells. A systematic literature search was performed using the following pre-defined criteria: treatment with pure compounds and metabolites (no extracts) at low concentrations that are close to their plasma concentrations. Differentially expressed genes were analyzed using bioinformatics tools to identify gene ontologies, networks, cellular pathways and interactions, as well as transcriptional and post-transcriptional regulators. The systematic literature search identified 54 differentially expressed genes at the mRNA level in in vitro models of cardiometabolic disease exposed to flavanols and their metabolites. Global bioinformatic analysis revealed that these genes are predominantly involved in inflammation, leukocyte adhesion and transendothelial migration, and lipid metabolism. We observed that, although the investigated cells responded differentially to flavanol exposure, the involvement of anti-inflammatory responses is a common mechanism of flavanol action. We also identified potential transcriptional regulators of gene expression: transcriptional factors, such as GATA2, NFKB1, FOXC1 or PPARG, and post-transcriptional regulators: miRNAs, such as mir-335-5p, let-7b-5p, mir-26b-5p or mir-16-5p. In parallel, we analyzed the nutrigenomic effects of flavanols in intestinal cells and demonstrated their predominant involvement in the metabolism of circulating lipoproteins. In conclusion, the results of this systematic analysis of the nutrigenomic effects of flavanols provide a more comprehensive picture of their molecular mechanisms of action and will support the future setup of genetic studies to pave the way for individualized dietary recommendations.

Item Type: Article
Impact Factor Value: 4.171
Subjects: Medical and Health Sciences > Basic medicine
Divisions: Faculty of Medical Science
Depositing User: Tatjana Ruskovska
Date Deposited: 17 Sep 2020 07:15
Last Modified: 17 Sep 2020 07:15

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