title: Epigenetic programming of adipose-derived stem cells in low birthweight individuals.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet - Section 7652, Tagensvej 20, DK-2200, Copenhagen, Denmark. christa.broholm@gmail.com.
authors.forename: Christa
authors.initials: C
authors.lastname: Broholm
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet - Section 7652, Tagensvej 20, DK-2200, Copenhagen, Denmark.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Olsson
authors.affiliation: Department of Clinical Sciences, Epigenetics and Diabetes, Lund University Diabetes Centre, CRC, Malmö, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Perfilyev
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet - Section 7652, Tagensvej 20, DK-2200, Copenhagen, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ninna S
authors.initials: NS
authors.lastname: Hansen
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet - Section 7652, Tagensvej 20, DK-2200, Copenhagen, Denmark.
authors.forename: Maren
authors.initials: M
authors.lastname: Schrölkamp
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet - Section 7652, Tagensvej 20, DK-2200, Copenhagen, Denmark.
authors.forename: Klaudia S
authors.initials: KS
authors.lastname: Strasko
authors.affiliation: Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Centre of Inflammation and Metabolism, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Scheele
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet - Section 7652, Tagensvej 20, DK-2200, Copenhagen, Denmark.|Danish Diabetes Academy, Odense, Denmark.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Ribel-Madsen
authors.affiliation: Steno Diabetes Center A/S, Gentofte, Denmark.
authors.forename: Brynjulf
authors.initials: B
authors.lastname: Mortensen
authors.affiliation: Steno Diabetes Center A/S, Gentofte, Denmark.
authors.forename: Sine W
authors.initials: SW
authors.lastname: Jørgensen
authors.affiliation: Department of Clinical Sciences, Epigenetics and Diabetes, Lund University Diabetes Centre, CRC, Malmö, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet - Section 7652, Tagensvej 20, DK-2200, Copenhagen, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Steno Diabetes Center A/S, Gentofte, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics; D052242:Adiponectin / Q000235:genetics; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism*; D000328:Adult; D001724:Birth Weight / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D056906:Cyclin T / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D006801:Humans; D008297:Male; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D050795:STAT2 Transcription Factor / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; C441622:CCNT2 protein, human; D056906:Cyclin T; D034741:RNA, Small Interfering; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human
keywords: Adipocytes; Adipogenesis; Adipose tissue; Cyclin T2; Epigenetics; Fetal programming; Low birthweight; Metabolic disease; Type 2 diabetes