Systematic Bioinformatic Analyses of Nutrigenomic Modifications by Polyphenols Associated with Cardiometabolic Health in Humans-Evidence from Targeted Nutrigenomic Studies

• Published in: Nutrients Vol. 13; no. 7; p. 2326
• Main Authors: Ruskovska, Tatjana, Budić-Leto, Irena, Corral-Jara, Karla Fabiola, Ajdžanović, Vladimir, Arola-Arnal, Anna, Bravo, Francisca Isabel, Deligiannidou, Georgia-Eirini, Havlik, Jaroslav, Janeva, Milkica, Kistanova, Elena, Kontogiorgis, Christos, Krga, Irena, Massaro, Marika, Miler, Marko, Milosevic, Verica, Morand, Christine, Scoditti, Egeria, Suárez, Manuel, Vauzour, David, Milenkovic, Dragan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2021; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; Adipocytes; Adult; AKT protein; Bioflavonoids; Bioinformatics; Blood cells; Blood pressure; cardiometabolic health; Cardiometabolic Risk Factors; Cholesterol; Computational Biology; Disease; DNA binding proteins; Female; Flavones; Flavonoids; Food and Nutrition; Gender; Gene expression; Gene regulation; Genes; Genetic transcription; Glucose; Health aspects; Health risks; human; Human populations; Humans; Inflammation; Insulin resistance; integrative bioinformatics; Intervention; Life Sciences; Lipid metabolism; Lipids; Low density lipoprotein; Male; MAP kinase; Metabolic Syndrome - genetics; Metabolic Syndrome - prevention & control; Metabolites; MicroRNA; MicroRNAs - blood; Middle Aged; miRNA; Molecular modelling; Nutrigenomics; Nutrition research; Nutritional Physiological Phenomena - genetics; Oxidative stress; Peripheral blood; Peroxisome proliferator-activated receptors; Polymerase chain reaction; Polyphenols; Polyphenols - pharmacology; Protective Agents - pharmacology; Real-Time Polymerase Chain Reaction; RelA protein; Risk analysis; Risk factors; RNA, Messenger - blood; Signal transduction; Signal Transduction - genetics; SIRT1 protein; Stat1 protein; systematic literature search; Transcription factors; Tumor necrosis factor; Type 2 diabetes; nutrigenomics; polyphenols; integrative bioinformatics; systematic literature search; cardiometabolic health; human
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13072326

Cardiometabolic disorders are among the leading causes of mortality in the human population. Dietary polyphenols exert beneficial effects on cardiometabolic health in humans. Molecular mechanisms, however, are not completely understood. Aiming to conduct in-depth integrative bioinformatic analyses to elucidate molecular mechanisms underlying the protective effects of polyphenols on cardiometabolic health, we first conducted a systematic literature search to identify human intervention studies with polyphenols that demonstrate improvement of cardiometabolic risk factors in parallel with significant nutrigenomic effects. Applying the predefined inclusion criteria, we identified 58 differentially expressed genes at mRNA level and 5 miRNAs, analyzed in peripheral blood cells with RT-PCR methods. Subsequent integrative bioinformatic analyses demonstrated that polyphenols modulate genes that are mainly involved in the processes such as inflammation, lipid metabolism, and endothelial function. We also identified 37 transcription factors that are involved in the regulation of polyphenol modulated genes, including RELA/NFKB1, STAT1, JUN, or SIRT1. Integrative bioinformatic analysis of mRNA and miRNA-target pathways demonstrated several common enriched pathways that include MAPK signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, focal adhesion, or PPAR signaling pathway. These bioinformatic analyses represent a valuable source of information for the identification of molecular mechanisms underlying the beneficial health effects of polyphenols and potential target genes for future nutrigenetic studies.