Josefine Jönsson
Forskningsadministratör
Circulating triglycerides are associated with human adipose tissue DNA methylation of genes linked to metabolic disease
Författare
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.
Avdelning/ar
- Diabetes - epigenetik
- EXODIAB: Excellence of Diabetes Research in Sweden
- Translationell muskelforskning
- Vaskulära sjukdomar - kliniska studier
- EpiHealth: Epidemiology for Health
Publiceringsår
2023-05-18
Språk
Engelska
Sidor
1875-1887
Publikation/Tidskrift/Serie
Human Molecular Genetics
Volym
32
Issue
11
Dokumenttyp
Artikel i tidskrift
Förlag
Oxford University Press
Ämne
- Medical Genetics
Nyckelord
- Humans
- Male
- Female
- DNA Methylation/genetics
- Triglycerides/genetics
- Insulin Resistance/genetics
- Epigenesis, Genetic/genetics
- Adipose Tissue/metabolism
Status
Published
Forskningsgrupp
- Diabetes - Epigenetics
- LUDC (Lund University Diabetes Centre)
- Translational Muscle Research
- Vascular Diseases - Clinical Research
ISBN/ISSN/Övrigt
- ISSN: 0964-6906