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

Broholm, Christa; Olsson, Anders H. LU ; Perfilyev, Alexander LU ; Hansen, Ninna S.; Schrölkamp, Maren; Strasko, Klaudia S.; Scheele, Camilla; Ribel-Madsen, Rasmus; Mortensen, Brynjulf and Jørgensen, Sine W., et al. (2016) In Diabetologia 59(12). p.2664-2673
Abstract

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... (More)

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.

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published
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keywords
Adipocytes, Adipogenesis, Adipose tissue, Cyclin T2, Epigenetics, Fetal programming, Low birthweight, Metabolic disease, Type 2 diabetes
in
Diabetologia
volume
59
issue
12
pages
10 pages
publisher
Springer Verlag
external identifiers
  • Scopus:84987618034
  • WOS:000387596300023
ISSN
0012-186X
DOI
10.1007/s00125-016-4099-9
language
English
LU publication?
yes
id
250d4506-cab6-4cf4-b8f3-01a7674e3c82
date added to LUP
2016-10-03 15:05:58
date last changed
2017-01-09 14:46:14
@article{250d4506-cab6-4cf4-b8f3-01a7674e3c82,
  abstract     = {<p>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.</p>},
  author       = {Broholm, Christa and Olsson, Anders H. and Perfilyev, Alexander and Hansen, Ninna S. and Schrölkamp, Maren and Strasko, Klaudia S. and Scheele, Camilla and Ribel-Madsen, Rasmus and Mortensen, Brynjulf and Jørgensen, Sine W. and Ling, Charlotte and Vaag, Allan},
  issn         = {0012-186X},
  keyword      = {Adipocytes,Adipogenesis,Adipose tissue,Cyclin T2,Epigenetics,Fetal programming,Low birthweight,Metabolic disease,Type 2 diabetes},
  language     = {eng},
  number       = {12},
  pages        = {2664--2673},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Epigenetic programming of adipose-derived stem cells in low birthweight individuals},
  url          = {http://dx.doi.org/10.1007/s00125-016-4099-9},
  volume       = {59},
  year         = {2016},
}