TY - JOUR
T1 - Effects of lifestyle interventions on epigenetic signatures of liver fat
T2 - Central randomized controlled trial
AU - Yaskolka Meir, Anat
AU - Keller, Maria
AU - Müller, Luise
AU - Bernhart, Stephan H.
AU - Tsaban, Gal
AU - Zelicha, Hila
AU - Rinott, Ehud
AU - Kaplan, Alon
AU - Gepner, Yftach
AU - Shelef, Ilan
AU - Schwarzfuchs, Dan
AU - Ceglarek, Uta
AU - Stadler, Peter
AU - Blüher, Matthias
AU - Stumvoll, Michael
AU - Kovacs, Peter
AU - Shai, Iris
N1 - Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Background and Aims: In the CENTRAL trial context, we found diverse liver fat dynamics in response to different dietary interventions. Epigenetic mechanisms may contribute to the intraindividual variation. Moreover, genetic factors are involved in developing nonalcoholic fatty-liver disease (NAFLD), a disease reflected by an increase in intrahepatic fat (IHF). In this exploratory analysis, we primarily aimed to examine the effect of lifestyle interventions on DNA-methylation of NAFLD related genes associated with IHF. Methods: For 120 participants from the CENTRAL trial, an 18-month regimen of either low-fat (LF) or Mediterranean-low carbohydrate (MED/LC) diets, with or without physical activity (PA+/PA−), was instructed. Magnetic resonance imaging was used to measure IHF%, which was analysed for association with CpG specific DNA-methylation levels of 41 selected candidate genes. Single-nucleotide polymorphisms known to be associated with NAFLD within the studied genes were genotyped by TaqMan assays. Results: At baseline, participants (92% men; body mass index = 30.2 kg/m2) had mean IHF of 10.7% (59% NAFLD). Baseline-IHF% was inversely correlated with DNA-methylation at individual CpGs within AC074286.1, CRACR2A, A2MP1, FARP1 (P <.05 for all multivariate models). FARP1 rs9584805 showed association with IHF, with the prevalence of NAFLD and baseline methylation level of the CpG site (cg00071727) associated with IHF%. Following 18-month lifestyle intervention, differential DNA-methylation patterns were observed between diets at cg14335324 annotated to A2MP1 (P =.04, LF vs. MED/LC), and differential DNA-methylation between PA groups within AC074286.1, CRACR2A, and FARP1 CpGs (P <.05 for all, PA−vs. PA+). Conclusions: This study suggests epigenetic markers for IHF and potential epigenetic remodeling after long-term lifestyle interventions.
AB - Background and Aims: In the CENTRAL trial context, we found diverse liver fat dynamics in response to different dietary interventions. Epigenetic mechanisms may contribute to the intraindividual variation. Moreover, genetic factors are involved in developing nonalcoholic fatty-liver disease (NAFLD), a disease reflected by an increase in intrahepatic fat (IHF). In this exploratory analysis, we primarily aimed to examine the effect of lifestyle interventions on DNA-methylation of NAFLD related genes associated with IHF. Methods: For 120 participants from the CENTRAL trial, an 18-month regimen of either low-fat (LF) or Mediterranean-low carbohydrate (MED/LC) diets, with or without physical activity (PA+/PA−), was instructed. Magnetic resonance imaging was used to measure IHF%, which was analysed for association with CpG specific DNA-methylation levels of 41 selected candidate genes. Single-nucleotide polymorphisms known to be associated with NAFLD within the studied genes were genotyped by TaqMan assays. Results: At baseline, participants (92% men; body mass index = 30.2 kg/m2) had mean IHF of 10.7% (59% NAFLD). Baseline-IHF% was inversely correlated with DNA-methylation at individual CpGs within AC074286.1, CRACR2A, A2MP1, FARP1 (P <.05 for all multivariate models). FARP1 rs9584805 showed association with IHF, with the prevalence of NAFLD and baseline methylation level of the CpG site (cg00071727) associated with IHF%. Following 18-month lifestyle intervention, differential DNA-methylation patterns were observed between diets at cg14335324 annotated to A2MP1 (P =.04, LF vs. MED/LC), and differential DNA-methylation between PA groups within AC074286.1, CRACR2A, and FARP1 CpGs (P <.05 for all, PA−vs. PA+). Conclusions: This study suggests epigenetic markers for IHF and potential epigenetic remodeling after long-term lifestyle interventions.
KW - DNA-methylation
KW - Diet
KW - genetic variation
KW - nonalcoholic fatty liver disease
KW - physical activity
UR - http://www.scopus.com/inward/record.url?scp=85106660339&partnerID=8YFLogxK
U2 - 10.1111/liv.14916
DO - 10.1111/liv.14916
M3 - Article
C2 - 33938135
AN - SCOPUS:85106660339
SN - 1478-3223
VL - 41
SP - 2101
EP - 2111
JO - Liver International
JF - Liver International
IS - 9
ER -