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Boczki, P.* ; Colombo, M.* ; Weiner, J.* ; Rapöhn, I. ; Lacher, M.* ; Kiess, W.* ; Hanschkow, M.* ; Körner, A. ; Landgraf, K.*

Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells.

Adipocyte 13:2290218 (2024)

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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Ahcy ; Adipocyte Progenitor Cells ; Adipogenesis ; Adipose Tissue ; Obesity; S-adenosylhomocysteine Hydrolase; Gene-expression; Ppar-gamma; Adenosine Dialdehyde; Dna Methylation; Obesity; Adenosylmethionine; Adipogenesis; Inflammation; Association

ISSN (print) / ISBN 2162-3945

e-ISSN 2162-397X

Journal Adipocyte

Quellenangaben Volume: 13, Issue: 1, Article Number: 2290218

Publisher Landes Bioscience

Publishing Place 530 Walnut Street, Ste 850, Philadelphia, Pa 19106 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)

Grants Medical Faculty at the University of Leipzig
German Diabetes Society
German Research Foundation for the Clinical Research Center 'Obesity Mechanisms'