Autor:innen:
A. Hoffmann (Leipzig, DE)
A. Yaskolka Meir (Boston, US)
T. Hagemann (Leipzig, DE)
L. Müller (Leipzig, DE)
B. Engelmann (Leipzig, DE)
S. Haange (Leipzig, DE)
U. Rolle-Kampczyk (Leipzig, DE)
G. Tsaban (Beer-Sheva, IL)
H. Zelicha (Leipzig, DE)
E. Rinott (Beer-Sheva, IL)
A. Kaplan (Beer-Sheva, IL)
I. Shelef (Beer-Sheva, IL)
M. Stumvoll (Leipzig, DE)
M. Blüher (Leipzig, DE)
L. Liang (Boston, US)
U. Ceglarek (Leipzig, DE)
B. Isermann (Leipzig, DE)
M. von Bergen (Leipzig, DE)
P. Kovacs (Leipzig, DE)
M. Keller (Leipzig, DE)
I. Shai (Beer-Sheva, IL)
Background: To highlight molecular mechanisms underlying the beneficial metabolic effects of a Mediterranean (MED) diet enriched in polyphenols and reduced in red/processed meat (greenMED), we analyzed its effects on methylome and transcriptome in the 18-month DIRECT PLUS randomized controlled trial.
Methods: The study included 260 participants (baseline BMI=31.2 kg/m2, age=51 years) initially randomized to one of the intervention arms: healthy dietary guidelines (HDG), MED (further 440mg polyphenols were provided by walnuts) and green-MED (further 1240mg polyphenols provided by walnuts, green tea and green duckweed shake). Blood methylome and transcriptome were analyzed at baseline and after the 18-month intervention using Illumina EPIC and RNA sequencing technologies.
Results: A total of 1,573 Differentially Methylated Regions (DMRs; false discovery rate (FDR < 5%) was found in the greenMED compared to the MED (177) and HDG (377) intervention. This corresponded to 1,753 Differentially Expressed Genes (DEGs; FDR < 5%) in the greenMED arm compared to MED (7) and HDG (738). Consistently, the highest number (6%) of epigenetic modulating genes was transcriptionally changed by the greenMED diet. Weighted Gene Co-Expression Network Analysis identified candidate genes in association with folic acid change and highlighted one module being negatively correlated with the polyphenol changes but positively with the superficial subcutaneous adipose area-, weight- and waist circumference-change after the greenMED diet.
Conclusions: Our findings suggest epigenetic key drivers such as folate mediating the prominent capacity of the greenMED diet to regulate individual’s epigenome but also indicate a direct effect of dietary polyphenols on the one-carbon metabolism.