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Josefine Jönsson

Research administrator

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Circulating triglycerides are associated with human adipose tissue DNA methylation of genes linked to metabolic disease

Author

  • Tina Rönn
  • Alexander Perfilyev
  • Josefine Jönsson
  • Karl-Fredrik Eriksson
  • Sine W Jørgensen
  • Charlotte Brøns
  • Linn Gillberg
  • Allan Vaag
  • Elisabet Stener-Victorin
  • Charlotte Ling

Summary, in English

Dysregulation of circulating lipids is a central element for the metabolic syndrome. However, it is not well established whether human subcutaneous adipose tissue is affected by or affect circulating lipids through epigenetic mechanisms. Hence, our aim was to investigate the association between circulating lipids and DNA methylation levels in human adipose tissue. DNA methylation and gene expression were analysed genome-wide in subcutaneous adipose tissue from two different cohorts, including 85 men and 93 women, respectively. Associations between DNA methylation and circulating levels of triglycerides, low-density lipoprotein, high-density lipoprotein and total cholesterol were analysed. Causal mediation analyses tested if adipose tissue DNA methylation mediates the effects of triglycerides on gene expression or insulin resistance. We found 115 novel associations between triglycerides and adipose tissue DNA methylation, e.g. in the promoter of RFS1, ARID2 and HOXA5 in the male cohort (P ≤ 1.1 × 10-7), and 63 associations, e.g. within the gene body of PTPRN2 and COL6A3 in the female cohort. We further connected these findings to altered mRNA expression levels in adipose tissue (e.g. HOXA5, IL11 and FAM45B). Interestingly, there was no overlap between methylation sites associated with triglycerides in men and the sites found in women, which points towards sex-specific effects of triglycerides on the epigenome. Finally, a causal mediation analysis provided support for adipose tissue DNA methylation as a partial mediating factor between circulating triglycerides and insulin resistance. This study identified novel epigenetic alterations in adipose tissue associated with circulating lipids. Identified epigenetic changes seem to mediate effects of triglycerides on insulin resistance.

Department/s

  • Diabetes - Epigenetics
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Translational Muscle Research
  • Vascular Diseases - Clinical Research
  • EpiHealth: Epidemiology for Health

Publishing year

2023-05-18

Language

English

Pages

1875-1887

Publication/Series

Human Molecular Genetics

Volume

32

Issue

11

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Medical Genetics

Keywords

  • Humans
  • Male
  • Female
  • DNA Methylation/genetics
  • Triglycerides/genetics
  • Insulin Resistance/genetics
  • Epigenesis, Genetic/genetics
  • Adipose Tissue/metabolism

Status

Published

Research group

  • Diabetes - Epigenetics
  • LUDC (Lund University Diabetes Centre)
  • Translational Muscle Research
  • Vascular Diseases - Clinical Research

ISBN/ISSN/Other

  • ISSN: 0964-6906