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

Nilsson, Emma LU orcid ; Vavakova, Magdalena LU ; Perfilyev, Alexander LU orcid ; Säll, Johanna LU orcid ; Jansson, Per-Anders ; Poulsen, Pernille ; Esguerra, Jonathan Lou S LU orcid ; Eliasson, Lena LU orcid ; Vaag, Allan LU and Göransson, Olga LU orcid , et al. (2021) In Diabetes 70(10). p.2402-2418
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
70
issue
10
pages
2402 - 2418
publisher
American Diabetes Association Inc.
external identifiers
  • scopus:85117878089
  • pmid:34315727
ISSN
1939-327X
DOI
10.2337/db20-0324
language
English
LU publication?
yes
id
b07578ab-47cc-4449-b7df-1cc42f457255
date added to LUP
2021-10-06 10:18:05
date last changed
2024-04-06 09:54:43
@article{b07578ab-47cc-4449-b7df-1cc42f457255,
  abstract     = {{<p>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.</p>}},
  author       = {{Nilsson, Emma and Vavakova, Magdalena and Perfilyev, Alexander and Säll, Johanna and Jansson, Per-Anders and Poulsen, Pernille and Esguerra, Jonathan Lou S and Eliasson, Lena and Vaag, Allan and Göransson, Olga and Ling, Charlotte}},
  issn         = {{1939-327X}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{2402--2418}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Differential DNA Methylation and Expression of miRNAs in Adipose Tissue From Twin Pairs Discordant for Type 2 Diabetes}},
  url          = {{http://dx.doi.org/10.2337/db20-0324}},
  doi          = {{10.2337/db20-0324}},
  volume       = {{70}},
  year         = {{2021}},
}