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Nutrigenomics and molecular nutrition

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



We aimed to investigate the effects of short-term hypocaloric diet-induced weight loss on DNA methylation profile in leukocytes from women with severe obesity.


Eleven women with morbid obesity (age: 36.9 ± 10.3 years; BMI: 58.5 ± 10.5 kg/m2) were assessed before and after 6 weeks of a hypocaloric dietary intervention. The participants were compared with women of average weight and the same age (age: 36.9 ± 11.8 years; BMI: 22.5 ± 1.6 kg/m2). Genome-wide DNA methylation analysis was performed in DNA extracted from peripheral blood leukocytes using the Infinium Human Methylation 450 BeadChip assay. Changes (Δβ) in the methylation level of each CpGs were calculated. A threshold with a minimum value of 10%, p < 0.001, for the significant CpG sites based on Δβ and a false discovery rate of <0.05 was set.


Dietary intervention changed the methylation levels at 16,064 CpG sites. These CpGs sites were related to cancer, cell cycle-related, MAPK, Rap1, and Ras signaling pathways. However, regardless of hypocaloric intervention, a group of 878 CpGs (related to 649 genes) remained significantly altered in obese women when compared with normal-weight women. Pathway enrichment analysis identified genes related to the cadherin and Wnt pathway, angiogenesis signaling, and p53 pathways by glucose deprivation.


A short-term hypocaloric intervention in patients with severe obesity partially restored the obesity-related DNA methylation pattern. Thus, the full change of obesity-related DNA methylation patterns could be proportional to the weight-loss rate in these patients after dietary interventions.

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Fig. 1: Clustering analysis of the differentially methylated CpG sites between severely obese versus normal-weight women.
Fig. 2: Clustering analysis of the differentially methylated CpG sites pre versus post intervention.
Fig. 3: Clustering analysis of the differentially methylated CpG sites between obese women versus women of average weight after the intervention.
Fig. 4: Integrated methylation data analysis.

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This study was supported by São Paulo Research Foundation (FAPESP) (grants #2016/06470-7, #2016/05638-1, and #2015/18669-0), Centro de Investigacion Biomedica En Red (CIBERobn) and grants (PI17/01287) from the Instituto de Salud Carlos III (ISCIII), Spain, co-financed by the European Regional Development Fund (FEDER). This research/work has also been supported by MINECO grants MTM2014-52876-R and MTM2017-82724-R, and by the Xunta de Galicia (Grupos de Referencia Competitiva ED431C-2016-015 and Centro Singular de Investigación de Galicia ED431G/01), all of them through the ERDF. ABC is funded by a research contract, “Miguel Servet” (CP17/00088), from the ISCIII, co-financed by the European Regional Development Fund.

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The authors’ responsibilities were as follows: CFN, MASP, and CBN contributed to the conception and design of the study. CC-O and JSM carried out the recruitment of the patients in the study. CFN, NYN, and MASP performed the laboratory analyses. CFN, AJ, and ABC analyzed the data, performed the statistical analysis, and drafted the manuscript. CFN and CBN wrote the manuscript. WSD, BG, and ABC critically revised the manuscript. All authors have read and approved the final version of the manuscript.

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Correspondence to A. B. Crujeiras or C. B. Nonino.

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This study was approved by the Hospital Ethics Committee of the School of Medicine of the University of São Paulo (CAAE:19442213.3.0000.5440) and was conducted in agreement with the Declaration of Helsinki. All participants gave informed written consent before their participation.

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Nicoletti, C.F., Cortes-Oliveira, C., Noronha, N.Y. et al. DNA methylation pattern changes following a short-term hypocaloric diet in women with obesity. Eur J Clin Nutr 74, 1345–1353 (2020).

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