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Alexander Perfilyev

Assistant researcher

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Differential DNA Methylation and Expression of miRNAs in Adipose Tissue From Twin Pairs Discordant for Type 2 Diabetes

Author

  • Emma Nilsson
  • Magdalena Vavakova
  • Alexander Perfilyev
  • Johanna Säll
  • Per-Anders Jansson
  • Pernille Poulsen
  • Jonathan Lou S Esguerra
  • Lena Eliasson
  • Allan Vaag
  • Olga Göransson
  • Charlotte Ling

Summary, in English

The prevalence of type 2 diabetes (T2D) is increasing worldwide, but current treatments have limitations. miRNAs may play a key role in the development of T2D and can be targets for novel therapies. Here, we examined whether T2D is associated with altered expression and DNA methylation of miRNAs using adipose tissue from 14 monozygotic twin pairs discordant for T2D. Four members each of the miR-30 and let-7-families were downregulated in adipose tissue of subjects with T2D versus control subjects, which was confirmed in an independent T2D case-control cohort. Further, DNA methylation of five CpG sites annotated to gene promoters of differentially expressed miRNAs, including miR-30a and let-7a-3, was increased in T2D versus control subjects. Luciferase experiments showed that increased DNA methylation of the miR-30a promoter reduced its transcription in vitro. Silencing of miR-30 in adipocytes resulted in reduced glucose uptake and TBC1D4 phosphorylation; downregulation of genes involved in demethylation and carbohydrate/lipid/amino acid metabolism; and upregulation of immune system genes. In conclusion, T2D is associated with differential DNA methylation and expression of miRNAs in adipose tissue. Downregulation of the miR-30 family may lead to reduced glucose uptake and altered expression of key genes associated with T2D.

Department/s

  • Diabetes - Epigenetics
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Protein Phosphorylation
  • Diabetes - Islet Cell Exocytosis

Publishing year

2021

Language

English

Pages

2402-2418

Publication/Series

Diabetes

Volume

70

Issue

10

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Epigenetics
  • Protein Phosphorylation
  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 1939-327X