Phytochemical-Rich Functional Diet Regulates Epigenetic Markers (DNA Methylation) Associated with Obesity and Insulin Resistance
https://doi.org/10.5281/zenodo.19438403
Keywords:
Phytochemicals, Functional Diet, DNA Methylation, Epigenetics, Obesity, Insulin Resistance, DNMT1, TET1, Histone Modifications, Metabolic Health, Obesity Epigenetics, Insulin Sensitivity, SLC2A4 Methylation, ADIPOQ Methylation, Polyphenol Functional Foods, EGCG, Quercetin, Genistein, Dietary Interventions Obesity, Epigenetic DietAbstract
Obesity and insulin resistance are characterized by chronic low-grade inflammation and epigenetic dysregulation, including hypermethylation of promoters in key metabolic genes such as SLC2A4, ADIPOQ, PPARγ, and LEP, leading to impaired glucose uptake, fatty acid metabolism, and systemic metabolic dysfunction. Bioactive phytochemicals—including quercetin, (-)-epigallocatechin gallate (EGCG), and genistein—act as natural inhibitors of DNA methyltransferases and can reverse these epigenetic modifications. In this study, a phytochemical-rich functional diet (PRFD) formulated in an enzymatically cross-linked soy-whey protein matrix was evaluated in a high-fat-diet-induced obese rat model. PRFD dose-dependently reduced promoter hypermethylation, suppressed DNMT1 activity, enhanced TET1-mediated demethylation, and promoted favourable histone modifications (increased H3K9ac, decreased H3K27me3). These molecular changes restored transcription of key metabolic genes, improving insulin sensitivity, glucose homeostasis, lipid profiles, and systemic inflammation. PRFD also mitigated oxidative stress, demonstrating a combinatorial mechanism linking metabolic and epigenetic restoration. These findings suggest that phytochemical-enriched functional diets can serve as systemic epigenetic modulators, offering a targeted strategy to counteract obesity-induced metabolic derangements.
