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Adipose tissue-derived microRNAs as epigenetic modulators of type 2 diabetes

Sehgal, Ratika ; Haacke, Neele ; Maguolo, Alice LU orcid ; Solari, Fiorella A. ; Jähnert, Markus ; Gottmann, Pascal ; Nilsson, Emma LU orcid ; Vaag, Allan LU ; Fischer-Posovszky, Pamela and Werberger, Anja , et al. (2025) In BMC Medicine 23(1).
Abstract

Background: White adipose tissue (WAT) dysfunction including an aberrant expression of miRNAs is strongly associated with the risk of developing type 2 diabetes (T2D), with limited evidence linking early changes in the WAT-derived miRNAs and T2D. The present study aims to identify early miRNome changes prognostic for T2D in mice and humans. Methods: Gonadal (g) WAT of diabetes-resistant and diabetes-prone mice were subjected to multi-omics analyses (transcriptome, miRNome, methylome, proteome). Metabolic phenotypes linked with T2D were correlated with adipose tissue miRNA expression and DNA methylation from 14 monozygotic twin pairs discordant for T2D. Plasma miRNA levels from females at high risk of developing T2D (TÜF study) were... (More)

Background: White adipose tissue (WAT) dysfunction including an aberrant expression of miRNAs is strongly associated with the risk of developing type 2 diabetes (T2D), with limited evidence linking early changes in the WAT-derived miRNAs and T2D. The present study aims to identify early miRNome changes prognostic for T2D in mice and humans. Methods: Gonadal (g) WAT of diabetes-resistant and diabetes-prone mice were subjected to multi-omics analyses (transcriptome, miRNome, methylome, proteome). Metabolic phenotypes linked with T2D were correlated with adipose tissue miRNA expression and DNA methylation from 14 monozygotic twin pairs discordant for T2D. Plasma miRNA levels from females at high risk of developing T2D (TÜF study) were included. Results: Adipose tissue of the diabetes-susceptible mice was less insulin sensitive with ~ 200 differentially expressed mature miRNAs compared to diabetes-resistant mice. Integrative analysis of miRNome-transcriptome-proteome identified 227 proteins involved in amino acid metabolism, inflammation, signalling pathways, and insulin resistance. More than 20 differentially expressed miRNAs are located in the imprinted region Dlk1-Gtl2 and Mest (miR-335) potentially regulated by DNA methylation. Imprinted miRNAs also exhibited similar alterations in adipose tissue from monozygotic twin pairs discordant for T2D, with miR-335 expression altered only in females. Moreover, plasma levels of miR-335-5p were negatively correlated with fasting blood glucose in females at high risk of developing T2D. Conclusions: Early alterations of WAT-derived miRNAs such as miR-335-5p could contribute to systemic metabolic changes associated with the risk of developing T2D.

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type
Contribution to journal
publication status
published
subject
keywords
Adipose tissue, Discordant monozygotic twins, Epigenetics, Imprinting, MicroRNA (miRNA), Multiomics, New Zealand Obese (NZO) mice, Type 2 diabetes (T2D)
in
BMC Medicine
volume
23
issue
1
article number
678
publisher
BioMed Central (BMC)
external identifiers
  • scopus:105024258840
  • pmid:41361331
ISSN
1741-7015
DOI
10.1186/s12916-025-04560-7
language
English
LU publication?
yes
id
4970639b-a125-43f1-9a5a-1566a76957a3
date added to LUP
2026-02-13 13:08:43
date last changed
2026-02-14 03:00:09
@article{4970639b-a125-43f1-9a5a-1566a76957a3,
  abstract     = {{<p>Background: White adipose tissue (WAT) dysfunction including an aberrant expression of miRNAs is strongly associated with the risk of developing type 2 diabetes (T2D), with limited evidence linking early changes in the WAT-derived miRNAs and T2D. The present study aims to identify early miRNome changes prognostic for T2D in mice and humans. Methods: Gonadal (g) WAT of diabetes-resistant and diabetes-prone mice were subjected to multi-omics analyses (transcriptome, miRNome, methylome, proteome). Metabolic phenotypes linked with T2D were correlated with adipose tissue miRNA expression and DNA methylation from 14 monozygotic twin pairs discordant for T2D. Plasma miRNA levels from females at high risk of developing T2D (TÜF study) were included. Results: Adipose tissue of the diabetes-susceptible mice was less insulin sensitive with ~ 200 differentially expressed mature miRNAs compared to diabetes-resistant mice. Integrative analysis of miRNome-transcriptome-proteome identified 227 proteins involved in amino acid metabolism, inflammation, signalling pathways, and insulin resistance. More than 20 differentially expressed miRNAs are located in the imprinted region Dlk1-Gtl2 and Mest (miR-335) potentially regulated by DNA methylation. Imprinted miRNAs also exhibited similar alterations in adipose tissue from monozygotic twin pairs discordant for T2D, with miR-335 expression altered only in females. Moreover, plasma levels of miR-335-5p were negatively correlated with fasting blood glucose in females at high risk of developing T2D. Conclusions: Early alterations of WAT-derived miRNAs such as miR-335-5p could contribute to systemic metabolic changes associated with the risk of developing T2D.</p>}},
  author       = {{Sehgal, Ratika and Haacke, Neele and Maguolo, Alice and Solari, Fiorella A. and Jähnert, Markus and Gottmann, Pascal and Nilsson, Emma and Vaag, Allan and Fischer-Posovszky, Pamela and Werberger, Anja and Birkenfeld, Andreas L. and Fritsche, Andreas and Häring, Hans Ulrich and Sickmann, Albert and Vogel, Heike and Ling, Charlotte and Ouni, Meriem and Schürmann, Annette}},
  issn         = {{1741-7015}},
  keywords     = {{Adipose tissue; Discordant monozygotic twins; Epigenetics; Imprinting; MicroRNA (miRNA); Multiomics; New Zealand Obese (NZO) mice; Type 2 diabetes (T2D)}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Medicine}},
  title        = {{Adipose tissue-derived microRNAs as epigenetic modulators of type 2 diabetes}},
  url          = {{http://dx.doi.org/10.1186/s12916-025-04560-7}},
  doi          = {{10.1186/s12916-025-04560-7}},
  volume       = {{23}},
  year         = {{2025}},
}