Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells
Paula Boczki,
Marco Colombo,
Juliane Weiner,
Inka Rapöhn,
Martin Lacher,
Wieland Kiess,
Martha Hanschkow,
Antje Körner,
Kathrin Landgraf
Affiliations
Paula Boczki
Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany
Marco Colombo
Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany
Juliane Weiner
Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany
Inka Rapöhn
Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany
Martin Lacher
Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany
Wieland Kiess
Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany
Martha Hanschkow
Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany
Antje Körner
Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany
Kathrin Landgraf
Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, Germany
ABSTRACTS-adenosyl-homocysteine-hydrolase (AHCY) plays an important role in the methionine cycle regulating cellular methylation levels. AHCY has been reported to influence proliferation and differentiation processes in different cell types, e.g. in cancer cells and mouse embryonic stem cells. In the development of adipose tissue, both the proliferation and differentiation of adipocyte progenitor cells (APCs) are important processes, which in the context of obesity are often dysregulated. To assess whether AHCY might also be involved in cell proliferation and differentiation of APCs, we investigated the effect of reduced AHCY activity on human and mouse APCs in vitro. We show that the inhibition of AHCY using adenosine dialdehyde (AdOx) and the knockdown of AHCY using gene-specific siRNAs reduced APC proliferation and number. Inhibition of AHCY further reduced APC differentiation into mature adipocytes and the expression of adipogenic differentiation markers. Global DNA methylation profiling in human APCs revealed that inhibition of AHCY is associated with alterations in CpG methylation levels of genes involved in fat cell differentiation and pathways related to cellular growth. Our findings suggest that AHCY is necessary for the maintenance of APC proliferation and differentiation and inhibition of AHCY alters DNA methylation processes leading to a dysregulation of the expression of genes involved in the regulation of these processes.
