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Sökning: onr:"swepub:oai:lup.lub.lu.se:250d4506-cab6-4cf4-b8f3-01a7674e3c82" > Epigenetic programm...

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

Broholm, Christa (författare)
Copenhagen University Hospital
Olsson, Anders H. (författare)
Copenhagen University Hospital
Perfilyev, Alexander (författare)
Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups
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Hansen, Ninna S. (författare)
University of Copenhagen
Schrölkamp, Maren (författare)
Copenhagen University Hospital
Strasko, Klaudia S. (författare)
Copenhagen University Hospital
Scheele, Camilla (författare)
Copenhagen University Hospital
Ribel-Madsen, Rasmus (författare)
Danish Diabetes Academy
Mortensen, Brynjulf (författare)
Steno Diabetes Center Copenhagen
Jørgensen, Sine W. (författare)
Steno Diabetes Center Copenhagen
Ling, Charlotte (författare)
Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups
Vaag, Allan (författare)
Steno Diabetes Center Copenhagen
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 (creator_code:org_t)
Springer, 2016
2016
Engelska 10 s.
Ingår i: Diabetologia. - : Springer. - 0012-186X. ; 59:12, s. 2664-2673
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Nyckelord

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

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