DNA methylation pattern changes following a short-term hypocaloric diet in women with obesity

Nicoletti, Carolina Ferreira; Cortes-Oliveira, Cristiana; Noronha, Natália Yumi; Pinhel, Marcela Augusta Souza; Dantas, Wagner Silva; Jácome, Amalia; Marchini, Júlio Sérgio; Gualano, Bruno; Crujeiras, Ana B.; Nonino, Carla Barbosa

doi:10.1038/s41430-020-0660-1

Cited by 26 publications

(20 citation statements)

References 40 publications

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“…35 In addition, weight loss therapies are also able to modulate the obesityrelated methylation profile. 28,30,59,60 In line with these results, weight loss therapies based dietary energy restriction were able to reverse the obesity-related methylation levels of ACE2 with a putative increase in the transcript levels. However, after 6 months of bariatric surgery, the methylation and transcript levels of ACE2 did no change respect to baseline, even though patients showed a weight loss higher than 20%.…”

Section: Discussionsupporting

confidence: 65%

“…Changes in methylation levels after weight loss therapies were explored using data sets of blood leukocyte‐derived DNA from patients with obesity underwent a VLCKD (PnK method ® ), 30 a short‐term hypocaloric diet 28 or bariatric surgery 29 . Methylation data were extracted from DNA samples of these patients before and 6 months after weight loss therapies that were hybridized to the Illumina Infinium MethylationEPIC BeadChip.…”

Section: Methodsmentioning

confidence: 99%

“…The DNA methylation profile of ACE2 was evaluated by analysing our different methylome data sets of SAT, VAT and PBMCs as published 21,[27][28][29] plus unpublished data, as described in the Figure S1. The methylome data were obtained through the hybridization of samples in the Illumina Infinium HumanMethylation450 BeadChip or the Illumina Infinium MethylationEPIC BeadChip (Illumina) depending on the cohort.…”

Section: Data Collection and Dna Methylation Assessmentmentioning

confidence: 99%

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Adipose tissue and blood leukocytes ACE2 DNA methylation in obesity and after weight loss

Izquierdo

Carreira

Boughanem

et al. 2021

Eur J Clin Investigation

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Background: Obesity was consistently associated with a poor prognosis in patients with COVID-19. Epigenetic mechanisms were proposed as the link between obesity and comorbidities risk.Aim: To evaluate the methylation levels of angiotensin-converting enzyme 2 (ACE2) gene, the main entry receptor of SARS-CoV-2, in different depots of adipose tissue (AT) and leukocytes (PBMCs) in obesity and after weight loss therapy based on a very-low-calorie ketogenic diet (VLCKD), a balanced hypocaloric diet (HCD) or bariatric surgery (BS).

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Section: Discussionsupporting

confidence: 65%

Section: Methodsmentioning

confidence: 99%

Section: Data Collection and Dna Methylation Assessmentmentioning

confidence: 99%

See 1 more Smart Citation

Adipose tissue and blood leukocytes ACE2 DNA methylation in obesity and after weight loss

Izquierdo

Carreira

Boughanem

et al. 2021

Eur J Clin Investigation

View full text Add to dashboard Cite

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“…In adults, weight loss has been shown to be associated with significantly different DNA methylation patterns [84][85][86]. Analyzing longitudinal trajectories of DNA methylation and BMI at various time points in the same population from birth to adolescence would help to understand further the biological relevance of DNA methylation level changes and patterns of change [26,87].…”

Section: Strengths and Limitationsmentioning

confidence: 99%

DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies

et al. 2020

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Background DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10−7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10−4; adolescence Penrichment = 2.10 × 10−7). Conclusions There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

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“…In particular, changes in body weight following diet and/or exercise-driven interventions are sparsely considered in epigenetic studies. Even the few studies available so far are strongly limited by short intervention times, small sample sizes, or, e.g., restricted to women only [44][45][46][47]. Further, it has to be acknowledged that many of the prior studies published on similar subjects did not analyze immune cell subtypes; thus, it cannot be excluded that some of the differences they found are a function of immune cell differences.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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 < 1 × 10−5). 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 < 1 × 10− 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.

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DNA methylation pattern changes following a short-term hypocaloric diet in women with obesity

Cited by 26 publications

References 40 publications

Adipose tissue and blood leukocytes ACE2 DNA methylation in obesity and after weight loss

Adipose tissue and blood leukocytes ACE2 DNA methylation in obesity and after weight loss

DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies

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

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