Original Article | Published:

Clinical Studies and Practice

Subcutaneous adipose tissue gene expression and DNA methylation respond to both short- and long-term weight loss

International Journal of Obesity volume 42, pages 412423 (2018) | Download Citation

Abstract

Background:

Few studies have examined both gene expression and DNA methylation profiles in subcutaneous adipose tissue (SAT) during long-term weight loss. Thus, molecular mechanisms in weight loss and regain remain elusive.

Participants/Methods:

We performed a 1-year weight loss intervention on 19 healthy obese participants (mean body mass index (BMI) 34.6 kg m−2) and studied longitudinal gene expression (Affymetrix Human Genome U133 Plus 2.0) and DNA methylation (Infinium HumanMethylation450 BeadChip) in SAT at 0, 5 and 12 months. To examine whether weight loss and acquired obesity produce reciprocal profiles, we verified our findings in 26 BMI-discordant monozygotic twin pairs.

Results:

We found altered expression of 69 genes from 0 to 5’ months (short-term) weight loss. Sixty of these genes showed reversed expression in acquired obesity (twins). Altogether 21/69 genes showed significant expression–DNA methylation correlations. Pathway analyses revealed increased high-density lipoprotein-mediated lipid transport characteristic to short-term weight loss. After the fifth month, two groups of participants evolved: weight losers (WLs) and weight regainers (WRs). In WLs five genes were differentially expressed in 5 vs 12 months, three of which significantly correlated with methylation. Signaling by insulin receptor pathway showed increased expression. We further identified 35 genes with differential expression in WLs from 0 to 12 months (long-term) weight loss, with 20 showing opposite expression patterns in acquired obesity, and 16/35 genes with significant expression–DNA methylation correlations. Pathway analyses demonstrated changes in signal transduction, metabolism, immune system and cell cycle. Notably, seven genes (UCHL1, BAG3, TNMD, LEP, BHMT2, EPDR1 and OSTM1) were found to be downregulated during both short- and long-term weight loss.

Conclusions:

Our study indicates short- and long-term weight loss influences in transcription and DNA methylation in SAT of healthy participants. Moreover, we demonstrate that same genes react in an opposite manner in weight loss and acquired obesity.

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Acknowledgements

We are grateful to all the participants for their invaluable contributions to the study. The Obesity Research Unit team and the staff at the Finnish Twin Cohort Study are acknowledged for their help in the collection of the data. We also thank Dr Milla Kibble for providing critical comments on the manuscript. This study was supported by the Academy of Finland (grants 307339, 251316, 259926, 297908, 266286, 265240 and 263278), the Sigrid Juselius Foundation, the University of Helsinki Research Funds, the Helsinki University Hospital Research Funds, the Paulo Foundation, the Finnish Cultural Foundation Southwest Finland Regional Fund, the Turku University Hospital Research Funds, the Academy of Finland Centre of Excellence in Research on Mitochondria, Metabolism and Disease (grant 272376), grants from Novo Nordisk Foundation, the Biomedicum Helsinki Foundation, the Finnish Diabetes Research Foundation, the Jalmari and Rauha Ahokas Foundation, the Finnish Foundation for Cardiovascular Research, EPITRAIN-FP7-PEOPLE-2012-ITN (grant 316758) and Doctoral Programme in Population Health, University of Helsinki. We are thankful to the Biomedicum Functional Genomics Unit ((FuGU), Helsinki, Finland) and the Microarray Consortium (Oslo, Norway) for running gene expression and DNA methylation microarrays, respectively.

Author contributions

KHP, AR and MO conceived and designed the study. KHP collected the biological samples and performed the clinical investigations. KHP and MO coordinated the study. SB and MO wrote the manuscript. KHP helped in drafting the manuscript and critically commented on it. SB performed the bioinformatics and the statistical analysis of the methylation and expression data and the clinical measurements. SK and KAV assisted in clinical examinations of the participants. SK and SH helped in collecting the samples and extracted the adipocytes. KAV was responsible for the functional imaging studies. JK was responsible for the twin cohort data collection, a subset of which served as the validation cohort. All authors participated in discussions related to analysis and interpretation and have read and approved the final manuscript. MO is the guarantor of this work and as such had full access to the data and takes responsibility for the integrity of the data and the accuracy of the data analyses.

Author information

Affiliations

  1. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

    • S Bollepalli
    • , J Kaprio
    •  & M Ollikainen
  2. Department of Public Health, University of Helsinki, Helsinki, Finland

    • S Bollepalli
    • , J Kaprio
    •  & M Ollikainen
  3. Obesity Research Unit, Research Programs Unit, University of Helsinki, Helsinki, Finland

    • S Kaye
    • , S Heinonen
    • , A Rissanen
    •  & K H Pietiläinen
  4. Endocrinology, Abdominal Center, Helsinki University Central Hospital, and University of Helsinki, Helsinki, Finland

    • S Kaye
    • , S Heinonen
    •  & K H Pietiläinen
  5. Turku PET Centre, Turku University Hospital, Turku, Finland

    • K A Virtanen

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to M Ollikainen.

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DOI

https://doi.org/10.1038/ijo.2017.245

Supplementary Information accompanies this paper on International Journal of Obesity website (http://www.nature.com/ijo)

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