Human Adipogenesis is Associated with Genome-Wide DNA Methylation and Gene-Expression Changes

Abstract

Aim: To define the genomic distribution and function of DNA methylation changes during human adipogenesis. Methods: We isolated adipocyte-derived stem cells from 13 individuals and analyzed genome-wide DNA methylation and gene expression in cultured adipocyte-derived stem cells and mature adipocytes. Results: We observed altered DNA methylation of 11,947 CpG sites and altered expression of 11,830 transcripts after differentiation. De novo methylation was observed across all genomic elements. Co-existence of genes with both altered expression and DNA methylation was found in genes important for cell cycle and adipokine signaling. Conclusion: Human adipogenesis is associated with significant DNA methylation changes across the entire genome and may impact regulation of cell cycle and adipokine signaling.

Keywords::

• adipogenesis
• adiponectin
• DNA methylation
• epigenetics
• stem cells

Author contributions

C Broholm, AH Olsson, A Vaag and C Ling conceived and designed the study, analyzed the data and wrote the paper. C Broholm and NS Hansen carried out cell studies. L Gillberg performed pyrosequencing. A Perfilyev, A Ali and AH Olsson conducted the bioinformatics analyses. B Mortensen collected the human cohorts. All co-authors revised the manuscript and approved the final version.

Financial & competing interests disclosure

Support has been provided from the Danish Council for Independent Research, the Novo Nordisk Foundation, the European Foundation for the Study of Diabetes, Rigshospitalet, the Aase Ejnar Danielsens Foundation, the Swedish Research Council, The Swedish Diabetes Foundation, Påhlsson foundation and Region Skåne (ALF). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

Support has been provided from the Danish Council for Independent Research, the Novo Nordisk Foundation, the European Foundation for the Study of Diabetes, Rigshospitalet, the Aase Ejnar Danielsens Foundation, the Swedish Research Council, The Swedish Diabetes Foundation, Påhlsson foundation and Region Skåne (ALF). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.