Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells
S-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 develo...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Adipocyte |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21623945.2023.2290218 |
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| author | Paula Boczki Marco Colombo Juliane Weiner Inka Rapöhn Martin Lacher Wieland Kiess Martha Hanschkow Antje Körner Kathrin Landgraf |
| author_facet | Paula Boczki Marco Colombo Juliane Weiner Inka Rapöhn Martin Lacher Wieland Kiess Martha Hanschkow Antje Körner Kathrin Landgraf |
| author_sort | Paula Boczki |
| collection | DOAJ |
| description | S-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. |
| format | Article |
| id | doaj-art-370ad1071ce543bb9d3c9c5ccc0b48fa |
| institution | OA Journals |
| issn | 2162-3945 2162-397X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Adipocyte |
| spelling | doaj-art-370ad1071ce543bb9d3c9c5ccc0b48fa2025-08-20T02:30:42ZengTaylor & Francis GroupAdipocyte2162-39452162-397X2024-12-0113110.1080/21623945.2023.2290218Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cellsPaula Boczki0Marco Colombo1Juliane Weiner2Inka Rapöhn3Martin Lacher4Wieland Kiess5Martha Hanschkow6Antje Körner7Kathrin Landgraf8Center for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, GermanyCenter for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, GermanyMedical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, GermanyHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, GermanyDepartment of Pediatric Surgery, University of Leipzig, Leipzig, GermanyCenter for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, GermanyCenter for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, GermanyCenter for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, GermanyCenter for Pediatric Research Leipzig (CPL), Hospital for Children & Adolescents, University of Leipzig, Leipzig, GermanyS-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.https://www.tandfonline.com/doi/10.1080/21623945.2023.2290218AHCYadipocyte progenitor cellsadipogenesisadipose tissueobesity |
| spellingShingle | Paula Boczki Marco Colombo Juliane Weiner Inka Rapöhn Martin Lacher Wieland Kiess Martha Hanschkow Antje Körner Kathrin Landgraf Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells Adipocyte AHCY adipocyte progenitor cells adipogenesis adipose tissue obesity |
| title | Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells |
| title_full | Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells |
| title_fullStr | Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells |
| title_full_unstemmed | Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells |
| title_short | Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells |
| title_sort | inhibition of ahcy impedes proliferation and differentiation of mouse and human adipocyte progenitor cells |
| topic | AHCY adipocyte progenitor cells adipogenesis adipose tissue obesity |
| url | https://www.tandfonline.com/doi/10.1080/21623945.2023.2290218 |
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