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

Cross-omics DNA methylation Folate Lifestyle Obesity Polyphenols Randomized controlled trial (RCT) mRNA expression

Journal

Metabolism: clinical and experimental
ISSN: 1532-8600
Titre abrégé: Metabolism
Pays: United States
ID NLM: 0375267

Informations de publication

Date de publication:
08 2023
Historique:
received: 20 02 2023
revised: 16 05 2023
accepted: 18 05 2023
medline: 5 7 2023
pubmed: 27 5 2023
entrez: 26 5 2023
Statut: ppublish

Résumé

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. Our study included 260 participants (baseline BMI = 31.2 kg/m 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 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.

Sections du résumé

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/m
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
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.

Identifiants

pubmed: 37236302
pii: S0026-0495(23)00198-1
doi: 10.1016/j.metabol.2023.155594
pii:
doi:

Substances chimiques

Polyphenols 0
Tea 0

Types de publication

Randomized Controlled Trial Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

155594

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest MB received honoraria as a consultant and speaker from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Lilly, Novo Nordisk, Novartis, and Sanofi. IrSh advised the Hinoman, Ltd. nutritional committee. All other authors report no conflict of interest.

Auteurs

Anne Hoffmann (A)

Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig 04103, Germany.

Anat Yaskolka Meir (AY)

The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, 84101 Beer-Sheva, Israel; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

Tobias Hagemann (T)

Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig 04103, Germany.

Paul Czechowski (P)

Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig 04103, Germany.

Luise Müller (L)

Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig 04103, Germany.

Beatrice Engelmann (B)

Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research - UFZ, 04318 Leipzig, Germany.

Sven-Bastiaan Haange (SB)

Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research - UFZ, 04318 Leipzig, Germany.

Ulrike Rolle-Kampczyk (U)

Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research - UFZ, 04318 Leipzig, Germany.

Gal Tsaban (G)

The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, 84101 Beer-Sheva, Israel; Soroka University Medical Center, 84101 Beer-Sheva, Israel.

Hila Zelicha (H)

The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, 84101 Beer-Sheva, Israel.

Ehud Rinott (E)

The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, 84101 Beer-Sheva, Israel.

Alon Kaplan (A)

The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, 84101 Beer-Sheva, Israel.

Ilan Shelef (I)

Soroka University Medical Center, 84101 Beer-Sheva, Israel.

Michael Stumvoll (M)

Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig 04103, Germany; Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig 04103, Germany; Deutsches Zentrum für Diabetesforschung e.V., 85764 Neuherberg, Germany.

Matthias Blüher (M)

Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig 04103, Germany; Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig 04103, Germany.

Liming Liang (L)

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

Uta Ceglarek (U)

Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Universitätsklinikum Leipzig, Leipzig University, 04103 Leipzig, Germany.

Berend Isermann (B)

Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Universitätsklinikum Leipzig, Leipzig University, 04103 Leipzig, Germany.

Martin von Bergen (M)

Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research - UFZ, 04318 Leipzig, Germany; Institute of Biochemistry, Faculty of Life Sciences, University of Leipzig, 04103 Leipzig, Germany.

Peter Kovacs (P)

Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig 04103, Germany.

Maria Keller (M)

Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig 04103, Germany; Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig 04103, Germany. Electronic address: maria.keller@helmholtz-muenchen.de.

Iris Shai (I)

The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, 84101 Beer-Sheva, Israel; Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig 04103, Germany; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: irish@bgu.ac.il.

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Classifications MeSH