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Alexander Perfilyev

Assistant researcher

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Epigenetic programming of adipose-derived stem cells in low birthweight individuals

Author

  • Christa Broholm
  • Anders H. Olsson
  • Alexander Perfilyev
  • Ninna S. Hansen
  • Maren Schrölkamp
  • Klaudia S. Strasko
  • Camilla Scheele
  • Rasmus Ribel-Madsen
  • Brynjulf Mortensen
  • Sine W. Jørgensen
  • Charlotte Ling
  • Allan Vaag

Summary, in English

Aims/hypothesis: Low birthweight (LBW) is associated with dysfunctions of adipose tissue and metabolic disease in adult life. We hypothesised that altered epigenetic and transcriptional regulation of adipose-derived stem cells (ADSCs) could play a role in programming adipose tissue dysfunction in LBW individuals. Methods: ADSCs were isolated from the subcutaneous adipose tissue of 13 normal birthweight (NBW) and 13 LBW adult men. The adipocytes were cultured in vitro, and genome-wide differences in RNA expression and DNA methylation profiles were analysed in ADSCs and differentiated adipocytes. Results: We demonstrated that ADSCs from LBW individuals exhibit multiple expression changes as well as genome-wide alterations in methylation pattern. Reduced expression of the transcription factor cyclin T2 encoded by CCNT2 may play a key role in orchestrating several of the gene expression changes in ADSCs from LBW individuals. Indeed, silencing of CCNT2 in human adipocytes decreased leptin secretion as well as the mRNA expression of several genes involved in adipogenesis, including MGLL, LIPE, PPARG, LEP and ADIPOQ. Only subtle genome-wide mRNA expression and DNA methylation changes were seen in mature cultured adipocytes from LBW individuals. Conclusions/interpretation: Epigenetic and transcriptional changes in LBW individuals are most pronounced in immature ADSCs that in turn may programme physiological characteristics of the mature adipocytes that influence the risk of metabolic diseases. Reduced expression of CCNT2 may play a key role in the developmental programming of adipose tissue.

Department/s

  • Diabetes - Epigenetics
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2016-12

Language

English

Pages

2664-2673

Publication/Series

Diabetologia

Volume

59

Issue

12

Document type

Journal article

Publisher

Springer

Topic

  • Cell and Molecular Biology

Keywords

  • Adipocytes
  • Adipogenesis
  • Adipose tissue
  • Cyclin T2
  • Epigenetics
  • Fetal programming
  • Low birthweight
  • Metabolic disease
  • Type 2 diabetes

Status

Published

Research group

  • Diabetes - Epigenetics

ISBN/ISSN/Other

  • ISSN: 0012-186X