TY - JOUR
T1 - Systematic bioinformatic analysis of nutrigenomic data of flavanols in cell models of cardiometabolic disease
AU - Ruskovska, Tatjana
AU - Massaro, Marika
AU - Carluccio, Maria Annunziata
AU - Arola-Arnal, Anna
AU - Muguerza, Begoña
AU - Vanden Berghe, Wim
AU - Declerck, Ken
AU - Bravo, Francisca Isabel
AU - Calabriso, Nadia
AU - Combet, Emilie
AU - Gibney, Eileen R.
AU - Gomes, Andreia
AU - Gonthier, Marie Paule
AU - Kistanova, Elena
AU - Krga, Irena
AU - Mena, Pedro
AU - Morand, Christine
AU - Nunes Dos Santos, Claudia
AU - De Pascual-Teresa, Sonia
AU - Rodriguez-Mateos, Ana
AU - Scoditti, Egeria
AU - Suárez, Manuel
AU - Milenkovic, Dragan
N1 - Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2020/6
Y1 - 2020/6
N2 - 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. This journal is
AB - 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. This journal is
UR - http://www.scopus.com/inward/record.url?scp=85087110675&partnerID=8YFLogxK
U2 - 10.1039/d0fo00701c
DO - 10.1039/d0fo00701c
M3 - Article
C2 - 32537624
AN - SCOPUS:85087110675
VL - 11
SP - 5040
EP - 5064
JO - Food and Function
JF - Food and Function
SN - 2042-6496
IS - 6
ER -