A study published within the journal Metabolism describes the effect of a polyphenol-rich Mediterranean food plan on epigenetic regulation.
Study: A polyphenol-rich green Mediterranean food plan enhances epigenetic regulatory potential: the DIRECT PLUS randomized controlled trial. Image Credit: Antonina Vlasova / Shutterstock
Background
Chronic low-grade inflammation is taken into account a serious hallmark of assorted metabolic diseases, including obesity. Subsequently, lifestyle interventions, comparable to a healthy food plan and physical activity, are vital in managing body weight and reducing morbidity and mortality risks related to metabolic diseases.
Plant-based polyphenols with high antioxidant properties are known to have useful effects on metabolism. Mechanistically, polyphenols inhibit key epigenetic regulators, comparable to DNA-methyltransferases (DNMTs) or methylenetetrahydrofolate reductase (MTHFR), to modulate one-carbon metabolism and methylation processes. Furthermore, folic acid and B vitamins as methyl donors play crucial roles in regulating DNA and histone methylases.
The Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed (DIRECT PLUS) has been conducted for 18 months to judge the metabolic impact of healthy dietary guidelines (HDG), the Mediterranean (MED) food plan, and a modified MED food plan enriched with polyphenols (green-MED).
The findings of this randomized controlled trial have revealed that each MED diets have a moderate impact on weight reduction and a robust impact on hepatic fat reduction. Specifically, the green-MED, which incorporates high amounts of walnuts and Mankai (duckweed or watermeal), has been found to cause the best reduction in waist circumference, low-density lipoprotein-cholesterol serum level, diastolic blood pressure, C- reactive protein, and visceral adipose tissue. Each walnut and Mankai are wealthy sources of folate and B vitamins.
In the present study, scientists have explored whether green-MED diet-mediated metabolic improvements observed within the trial are related to its impact on genome-wide DNA methylation and mRNA expression patterns.
Study design
The study population included 260 participants (average age: 51 years; body mass index: 31 Kg/m2) from the DIRECT PLUS trial. They were randomly categorized into three intervention groups, including the HDG, MED food plan, and green-MED food plan groups. While the MED food plan included 440 mg of polyphenols moreover provided by walnuts, the green-MED food plan included 1240 mg of polyphenols moreover provided by walnuts, green tea, and Mankai.
Blood samples collected from the participants were analyzed for genome-wide DNA methylation and mRNA expression patterns at baseline and after the completion of the 18-month intervention period.
Necessary observations
The evaluation of genome-wide DNA methylation patterns before and after the dietary interventions identified 1,573 differentially methylated regions within the green-MED group, 377 within the HDG group, and 174 within the MED group. These findings corresponded to 1753 differentially expressed genes within the green-MED group, 738 within the HDG group, and only 7 within the MED group.
The consumption of a polyphenol-rich green-MED food plan for 18 months resulted in significantly higher levels of folic acid and vitamin B-12 within the serum in comparison with other dietary interventions. The increased levels of folic acid and vitamin B-12 observed within the MED group participants at baseline could possibly be attributed to lower levels of epigenetic changes observed on this group after the dietary intervention.
The high amounts of walnuts, green tea, and Mankai within the green-MED food plan showed a direct association with the increased levels of one-carbon precursors (folic acid and vitamin B-12) in participants consuming this particular food plan. These observations collectively indicate that green-MED diet-mediated changes in DNA methylation patterns are related to increased serum levels of folic acid and vitamin B-12.
Along with having a considerable effect on one-carbon precursors related to de novo methylation processes, a polyphenol-rich green-MED food plan showed a direct effect on the methylation and transcription of genes encoding epigenetic modulators, including lysine demethylase 2B, lysine demethylase 5B, and histone lysine methyltransferase.
Weighted Cluster Network Evaluation
The study conducted a Weighted Cluster Network evaluation to discover key drivers of phenotypic changes related to green-MED food plan consumption. Three essential modules containing many of the differentially methylated region genes were identified. Of those modules, one was significantly related to C-reactive protein, folic acid, interleukin 6 (IL-6), and alter in deep-subcutaneous adipose tissue area; one was related to waist circumference; and one was related to waist circumference and body weight change.
In the primary module, the mRNA expression of the KIR3DS1 gene showed a negative association with changes in polyphenols but a positive association with changes in superficial-subcutaneous adipose tissue area, body weight, and waist circumference. KIR3DS1 is a killer cell immunoglobulin-like receptor related to autoimmune diseases.
This module also included the differentially methylated region gene Cystathionine Beta-Synthase, an enzyme answerable for reducing homocysteine levels. The mRNA expression of this gene was related to changes in polyphenols.
Study significance
The study highlights that a polyphenol-rich MED food plan can significantly regulate DNA methylation patterns by increasing key epigenetic drivers comparable to folic acid and vitamin B-12. Moreover, polyphenols present within the food plan have high potency in regulating one-carbon metabolism with consequences in autoimmune responses.
Source
Hoffmann A. 2023. A polyphenol-rich green Mediterranean food plan enhances epigenetic regulatory potential: the DIRECT PLUS randomized controlled trial. Metabolism. https://www.metabolismjournal.com/article/S0026-0495(23)00198-1/fulltext