A key role of polyamine metabolism in adipose tissue homeostasis that regulates obesity
Mund C, Sinha A, Aderhold A, Mateska I, Hagag E, Traikov S, Gercken B, Soto A, Pollock J, Arndt L, Wölk M, Werner N, Fodelianaki G, Subramanian P, Chung KJ, Grossklaus S, Langner M, Elgendy M, Grinenko T, Wielockx B, Dahl A, Gericke M, Blüher M, Coskun Ü, Vöhringer D, Fedorova M, Peitzsch M, Murray PJ, Chavakis T, Alexaki VI (2025)
Publication Type: Journal article
Publication year: 2025
Journal
Book Volume: 172
Article Number: 156358
DOI: 10.1016/j.metabol.2025.156358
Abstract
Background and aims: Adipose tissue function is integral to systemic metabolic homeostasis. Excessive adipose tissue growth is associated with development of chronic low-grade inflammation and whole body dysmetabolism. The cell metabolic pathways regulating adipose tissue growth and homeostasis are little understood. Here we studied the role of polyamine metabolism in adipose tissue (patho)physiology. Methods: We generated mice with global and adipocyte progenitor (AP)-specific Antizyme inhibitor 2 (AZIN2) deficiency and performed diet-induced obesity studies. APs were isolated from the subcutaneous and gonadal adipose tissue of mice and cultured. Results: Polyamine metabolism components, including AZIN2, were highly expressed in APs and their expression in the adipose tissue was downregulated with obesity. IL4 induced Azin2 expression in APs. AZIN2 facilitated polyamine synthesis and acetylation, and regulated total acetyl-CoA levels in APs. AZIN2 deficiency upregulated histone acetylation in genes related to lipid metabolism. Azin2−/− APs committed more efficiently to adipogenesis in vivo and in vitro, and were more prone to senescence compared to wild-type counterparts. Upon diet-induced obesity, global and AP-specific AZIN2 deficiency in mice provoked AP depletion, adipocyte hypertrophy, obesity, inflammation, glucose intolerance and insulin resistance. In human adipose tissue, AZIN2 expression strongly correlated with expression of progenitor markers. Conclusions: Altogether, we identified AZIN2 as a novel AP marker that regulates AP fate and preserves adipose tissue health.
Authors with CRIS profile
Involved external institutions
Universitätsklinikum Carl Gustav Carus Dresden
Germany (DE)
Universität Leipzig
Germany (DE)
Technische Universität Dresden
Germany (DE)
Universitätsklinikum Leipzig
Germany (DE)
Max-Planck-Institut für Biochemie / Max Planck Institute of Biochemistry
Germany (DE)
Germany (DE)
Universität Leipzig
Germany (DE)
Technische Universität Dresden
Germany (DE)
Universitätsklinikum Leipzig
Germany (DE)
Max-Planck-Institut für Biochemie / Max Planck Institute of Biochemistry
Germany (DE)
How to cite
APA:
Mund, C., Sinha, A., Aderhold, A., Mateska, I., Hagag, E., Traikov, S.,... Alexaki, V.I. (2025). A key role of polyamine metabolism in adipose tissue homeostasis that regulates obesity. Metabolism-Clinical and Experimental, 172. https://doi.org/10.1016/j.metabol.2025.156358
MLA:
Mund, Christine, et al. "A key role of polyamine metabolism in adipose tissue homeostasis that regulates obesity." Metabolism-Clinical and Experimental 172 (2025).
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