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Annotation of Plant Gene Function via Combined Genomics, Metabolomics and Informatics
Published on: June 17, 2012
Systematic bioinformatic analysis of nutrigenomic data of flavanols in cell models of cardiometabolic disease
Tatjana Ruskovska1, Marika Massaro2, Maria Annunziata Carluccio2
1Faculty of Medical Sciences, Goce Delcev University, Stip, North Macedonia.
Abstract:
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.
Insights
Flavanols, found in certain foods, impact gene expression related to inflammation and lipid metabolism in cells crucial for cardiometabolic health. This research clarifies their molecular actions, aiding personalized nutrition strategies.
Area of Science:
- Nutrigenomics
- Molecular Biology
- Cardiovascular Research
Background:
- Flavanol consumption benefits cardiometabolic health.
- Molecular mechanisms, particularly gene regulation by flavanols in relevant cell types, remain unclear.
- Systematic analysis is needed to understand flavanol's impact on gene expression in cardiometabolic disease.
Purpose of the Study:
- To systematically review and bioinformatically analyze genes affected by flavanols in key cardiometabolic cell types.
- To identify molecular pathways, regulators, and common mechanisms of flavanol action.
- To investigate flavanols' nutrigenomic effects in intestinal cells and their role in lipoprotein metabolism.
Main Methods:
- Systematic literature review of flavanol and metabolite treatments on in vitro models.
- Bioinformatic analysis of differentially expressed genes (DEGs) at mRNA level.
- Identification of gene ontologies, networks, pathways, and regulators (transcription and post-transcription).
Main Results:
- Identified 54 DEGs in hepatocytes, adipocytes, endothelial, smooth muscle, and immune cells.
- Genes primarily involved in inflammation, leukocyte adhesion, transendothelial migration, and lipid metabolism.
- Common anti-inflammatory mechanisms observed across cell types; identified key transcriptional (GATA2, NFKB1, FOXC1, PPARG) and post-transcriptional (miRNAs) regulators.
- Flavanols influence intestinal cell lipoprotein metabolism.
Conclusions:
- This study provides a comprehensive overview of flavanols' nutrigenomic effects.
- Identified molecular mechanisms and regulators of flavanol action in cardiometabolic health.
- Findings support future genetic studies for personalized dietary recommendations.
