Dataset Information

DNA methylation signature in blood mirrors successful weight-loss during lifestyle interventions: the CENTRAL trial.

ABSTRACT:

Background

One of the major challenges in obesity treatment is to explain the high variability in the individual's response to specific dietary and physical activity interventions. With this study, we tested the hypothesis that specific DNA methylation changes reflect individual responsiveness to lifestyle intervention and may serve as epigenetic predictors for a successful weight-loss.

Methods

We conducted an explorative genome-wide DNA methylation analysis in blood samples from 120 subjects (90% men, mean?±?SD age?=?49?±?9?years, body mass-index (BMI)?=?30.2?±?3.3?kg/m²) from the 18-month CENTRAL randomized controlled trial who underwent either Mediterranean/low-carbohydrate or low-fat diet with or without physical activity.

Results

Analyses comparing male subjects with the most prominent body weight-loss (responders, mean weight change -?16%) vs. non-responders (+?2.4%) (N?=?10 each) revealed significant variation in DNA methylation of several genes including LRRC27, CRISP2, and SLFN12 (all adj. P?-5). Gene ontology analysis indicated that biological processes such as cell adhesion and molecular functions such as calcium ion binding could have an important role in determining the success of interventional therapies in obesity. Epigenome-wide association for relative weight-loss (%) identified 15 CpGs being negatively correlated with weight change after intervention (all combined P?-?4) including new and also known obesity candidates such as NUDT3 and NCOR2. A baseline DNA methylation score better predicted successful weight-loss [area under the curve (AUC) receiver operating characteristic (ROC)?=?0.95-1.0] than predictors such as age and BMI (AUC ROC?=?0.56).

Conclusions

Body weight-loss following 18-month lifestyle intervention is associated with specific methylation signatures. Moreover, methylation differences in the identified genes could serve as prognostic biomarkers to predict a successful weight-loss therapy and thus contribute to advances in patient-tailored obesity treatment.

SUBMITTER: Keller M

PROVIDER: S-EPMC7670623 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

DNA methylation signature in blood mirrors successful weight-loss during lifestyle interventions: the CENTRAL trial.

Keller Maria M Yaskolka Meir Anat A Bernhart Stephan H SH Gepner Yftach Y Shelef Ilan I Schwarzfuchs Dan D Tsaban Gal G Zelicha Hila H Hopp Lydia L Müller Luise L Rohde Kerstin K Böttcher Yvonne Y Stadler Peter F PF Stumvoll Michael M Blüher Matthias M Kovacs Peter P Shai Iris I

Genome medicine 20201116 1

<h4>Background</h4>One of the major challenges in obesity treatment is to explain the high variability in the individual's response to specific dietary and physical activity interventions. With this study, we tested the hypothesis that specific DNA methylation changes reflect individual responsiveness to lifestyle intervention and may serve as epigenetic predictors for a successful weight-loss.<h4>Methods</h4>We conducted an explorative genome-wide DNA methylation analysis in blood samples from ...[more]

PMID: 33198820

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Project description:BackgroundOver the past decades, there has been an increase in overweight and obesity in women of childbearing age, as well as the general population. Overweight and obesity are related to a later, increased risk of type 2 diabetes and cardiovascular diseases. Increasing weight between pregnancies has a negative impact on the development of the fetus in a subsequent pregnancy. It is also related to long-term obesity and overweight for the woman. Accordingly, weight control in women of the childbearing age is important for both women and their offspring. Information and communication technology (ICT) has become an integrated part of many peoples' lives, and it has the potential to prevent disease. In this systematic review, we summarize the evidence from randomized controlled trials to compare effects of different ICT-based interventions to support postpartum women to achieve weight loss.MethodsA systematic search was performed in PubMed, Embase, PsycInfo, CINAHL, Web of Science, Scopus, and Cochrane, searching on terms, such as postpartum, weight loss, telemedicine, and randomized controlled trials. Two independent researchers undertook study selection and data extraction. Results were reported narratively. The systematic review only included studies that were randomized controlled trials.ResultsEight studies were included in the systematic review. All of them were characterized by applying one or more ICT components to assist postpartum women in weight control, and had weight loss as an outcome measure. A significant difference was found in weight loss between control group and intervention group in the majority of the studies. However, five of the studies had a relatively short follow-up period (40 days to 16 weeks), six of the studies had a relatively small sample size (18 to 66 women), and half of the studies indicated challenges with adherence to the interventions over time.ConclusionICT-based interventions can support postpartum women to achieve a healthy lifestyle and weight control. Future studies should focus on larger sample sizes, longer follow-up periods, and adherence to the interventions.Systematic review registrationPROSPERO CRD42018080731.

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Project description:BackgroundThioredoxin Interacting Protein (TXNIP) functions as a master regulator for glucose homeostasis. Hypomethylation at the 5'-cytosine-phosphate-guanine-3' (CpG) site cg19693031 of TXNIP has been consistently related to islet dysfunction, hyperglycemia, and type 2 diabetes. DNA methylation (DNAm) may reveal the missing mechanistic link between obesity and type 2 diabetes. We hypothesize that baseline DNAm level at TXNIP in blood may be associated with glycemic traits and their changes in response to weight-loss diet interventions.MethodsWe included 639 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss diet intervention. Baseline blood DNAm levels were profiled by high-resolution methylC-capture sequencing. We defined the regional DNAm level of TXNIP as the average methylation level over CpGs within 500 bp of cg19693031. Generalized linear regression models were used for main analyses.ResultsWe found that higher regional DNAm at TXNIP was significantly correlated with lower fasting glucose, HbA1c, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at baseline (P < 0.05 for all). Significant interactions were observed between dietary protein intake and DNAm on changes in insulin (P-interaction = 0.007) and HOMA-IR (P-interaction = 0.009) at 6 months. In participants with the highest tertile of regional DNAm at TXNIP, average protein (15%) intake was associated with a greater reduction in insulin (β: -0.14; 95% CI: -0.24, -0.03; P = 0.011) and HOMA-IR (β: -0.15; 95% CI: -0.26, -0.03; P = 0.014) than high protein (25%) intake, whereas no significant associations were found in those with the lower tertiles (P > 0.05). The interaction was attenuated to be non-significant at 2 years, presumably related to decreasing adherence to the diet intervention.ConclusionsOur data indicate that higher regional DNAm level at TXNIP was significantly associated with better fasting glucose, HbA1c, and HOMA-IR; and people with higher regional DNAm levels benefited more in insulin and HOMA-IR improvement by taking the average-protein weight-loss diet.

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Dataset Information

DNA methylation signature in blood mirrors successful weight-loss during lifestyle interventions: the CENTRAL trial.

Background

Methods

Results

Conclusions

Publications

DNA methylation signature in blood mirrors successful weight-loss during lifestyle interventions: the CENTRAL trial.

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