Epigenetic programming of adipose-derived stem cells in low birthweight individuals
Open accessAbstract
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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Human CCNT2 knockout adipocytes have altered adipogenesis gene expression.
“Human CCNT2 knockout adipocytes have altered adipogenesis gene expression and decreased secretion of the hunger inhibiting hormone leptin, which is consistent with increased BFP [45].”
From Multi-trait association studies discover pleiotropic loci between Alzheimer’s disease and cardiometabolic traits (2021) · cites this paper as [45]
In “CCNT2 and STAT2 play a role in human adipogenesis,” siRNA silencing of CCNT2 in human donor-derived cells decreased expression of five selected adipogenic genes. The source studied knockdown, not knockout adipocytes; it also reports decreased leptin secretion after silencing. (LLM, conf=0.88)
Experimental — accuracy not yet measuredHuman CCNT2 knockout adipocytes have decreased secretion of the hunger inhibiting hormone leptin.
“Human CCNT2 knockout adipocytes have altered adipogenesis gene expression and decreased secretion of the hunger inhibiting hormone leptin, which is consistent with increased BFP [45].”
From Multi-trait association studies discover pleiotropic loci between Alzheimer’s disease and cardiometabolic traits (2021) · cites this paper as [45]
In “CCNT2 and STAT2 play a role in human adipogenesis,” the paper reports a modest but significant decrease in leptin secretion from human adipocytes after CCNT2 silencing. It used siRNA knockdown, not CCNT2 knockout, so the claim misidentifies the intervention. (LLM, conf=0.90)
Experimental — accuracy not yet measuredCCNT2 has been shown to be important in adipose biology.
“CCNT2 has been shown to be important in adipose biology [45].”
From Multi-trait association studies discover pleiotropic loci between Alzheimer’s disease and cardiometabolic traits (2021) · cites this paper as [45]
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Cites
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New genetic loci link adipose and insulin biology to body fat distribution
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Research works printed but not linked: 3
- Whincup PH, Kaye SJ, Owen CG et al (2008) Birth weight and risk of type 2 diabetes: a systematic review. JAMA 300:2886-2897
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Epigenetic Programming and Fetal Metabolic Programming
Zhu, Z., Cao, F., & Li, X. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00764 · Cited by 158 · see citing works
Lurbe, E., & Ingelfinger, J. (2021) · Hypertension · doi:10.1161/hypertensionaha.120.14592 · Cited by 106 · see citing works
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- Authors
- Broholm, C., Olsson, A. H., Perfilyev, A., Hansen, N. S., Schrölkamp, M., Strasko, K. S., Scheele, C., Ribel-Madsen, R., Mortensen, B., Jørgensen, S. W., Ling, C., & Vaag, A.
- Affiliations
- Rigshospitalet (DK)
- Lund University (SE)
- University of Copenhagen (DK)
- Steno Diabetes Centers (DK)
- Corresponding author
- Broholm, Christa
- Venue
- Diabetologia
- Published
- 2016-09-14
- Volume
- 59
- Issue
- 12
- Pages
- 2664-2673
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2518686386
- Cited by
- 43
- References
- 2
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2022: 2 · 2021: 10 · 2020: 2 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 1
- FWCI
- 8.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Danish Diabetes Academy
- European Foundation for the Study of Diabetes
- Aase og Ejnar Danielsens Fond
- Novo Nordisk
- Danmarks Frie Forskningsfond
- Rigshospitalet
- European Association for the Study of Diabetes
- Novo Nordisk Fonden (NNF15OC0016534)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- low birth weight, adipose-derived stem cells, epigenetic programming, DNA methylation, transcriptional regulation, adipogenesis, leptin secretion, metabolic disease risk
- MeSH terms
- Adipose Tissue, Adult, Birth Weight, Cells, Cultured, Humans, Male, Stem Cells, Adipocytes, DNA Methylation, RNA, Small Interfering, Epigenesis, Genetic, Adipogenesis, STAT2 Transcription Factor, Adiponectin, Young Adult, Cyclin T, Real-Time Polymerase Chain Reaction
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