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Hoffmann, A. ; Meir, A.Y.* ; Hagemann, T. ; Czechowski, P. ; Müller, L.* ; Engelmann, B.* ; Haange, S.B.* ; Rolle-Kampczyk, U.* ; Tsaban, G.* ; Zelicha, H.* ; Rinott, E.* ; Kaplan, A.* ; Shelef, I.* ; Stumvoll, M. ; Blüher, M. ; Liang, L.* ; Ceglarek, U.* ; Isermann, B.* ; von Bergen, M.* ; Kovacs, P.* ; Keller, M. ; Shai, I.*

A polyphenol-rich green Mediterranean diet enhances epigenetic regulatory potential: The DIRECT PLUS randomized controlled trial.

Metabolism 145:155594 (2023)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
BACKGROUND: The capacity of a polyphenol-enriched diet to modulate the epigenome in vivo is partly unknown. Given the beneficial metabolic effects of a Mediterranean (MED) diet enriched in polyphenols and reduced in red/processed meat (green-MED), as previously been proven by the 18-month DIRECT PLUS randomized controlled trial, we analyzed the effects of the green-MED diet on methylome and transcriptome levels to highlight molecular mechanisms underlying the observed metabolic improvements. METHODS: Our study included 260 participants (baseline BMI = 31.2 kg/m2, age = 5 years) of the DIRECT PLUS trial, initially randomized to one of the intervention arms: A. healthy dietary guidelines (HDG), B. MED (440 mg polyphenols additionally provided by walnuts), C. green-MED (1240 mg polyphenols additionally provided by walnuts, green tea, and Mankai: green duckweed shake). Blood methylome and transcriptome of all study subjects were analyzed at baseline and after completing the 18-month intervention using Illumina EPIC and RNA sequencing technologies. RESULTS: A total of 1573 differentially methylated regions (DMRs; false discovery rate (FDR) < 5 %) were found in the green-MED compared to the MED (177) and HDG (377) diet participants. This corresponded to 1753 differentially expressed genes (DEGs; FDR < 5 %) in the green-MED intervention compared to MED (7) and HDG (738). Consistently, the highest number (6 %) of epigenetic modulating genes was transcriptionally changed in subjects participating in the green-MED intervention. Weighted cluster network analysis relating transcriptional and phenotype changes among participants subjected to the green-MED intervention identified candidate genes associated with serum-folic acid change (all P < 1 × 10-3) and highlighted one module including the KIR3DS1 locus, being negatively associated with the polyphenol changes (e.g. P < 1 × 10-4), but positively associated with the MRI-assessed superficial subcutaneous adipose area-, weight- and waist circumference- 18-month change (all P < 0.05). Among others, this module included the DMR gene Cystathionine Beta-Synthase, playing a major role in homocysteine reduction. CONCLUSIONS: The green-MED high polyphenol diet, rich in green tea and Mankai, renders a high capacity to regulate an individual's epigenome. Our findings suggest epigenetic key drivers such as folate and green diet marker to mediate this capacity and indicate a direct effect of dietary polyphenols on the one‑carbon metabolism.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cross-omics ; Dna Methylation ; Folate ; Lifestyle ; Obesity ; Polyphenols ; Randomized Controlled Trial (rct) ; Mrna Expression; Dna Methylation; Weight; Inflammation; Folate
ISSN (print) / ISBN 0026-0495
e-ISSN 1532-8600
Zeitschrift Metabolism: clinical and experimental
Quellenangaben Band: 145, Heft: , Seiten: , Artikelnummer: 155594 Supplement: ,
Verlag Elsevier
Verlagsort 1600 John F Kennedy Boulevard, Ste 1800, Philadelphia, Pa 19103-2899 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Förderungen UFZ
Council for Higher Education
California Walnuts Commission
Israel Ministry of Science and Technology
Israel Ministry of Health
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Deutsches Zentrum fur Diabetesforschung
Free State of Saxony