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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, K.J.* ; Grossklaus, S.* ; Langner, M.* ; Elgendy, M.* ; Grinenko, T.* ; Wielockx, B.* ; Dahl, A.* ; Gericke, M.* ; Blüher, M.* ; Coskun, Ü. ; Voehringer, D.* ; Fedorova, M.* ; Peitzsch, M.* ; Murray, P.J.* ; Chavakis, T. ; Alexaki, V.I.*

A key role of polyamine metabolism in adipose tissue homeostasis that regulates obesity.

Metabolism 172:156358 (2025)
Publ. Version/Full Text DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Azin2 ; Adipocyte Progenitors ; Adipose Tissue ; Obesity ; Polyamine Metabolism; Adipocyte Progenitor Cells; Enrichment Analysis; Structural Basis; Web Server; Fat; Adipogenesis; Identification; Inflammation; Activation; Expression
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 0026-0495
e-ISSN 1532-8600
Journal Metabolism: clinical and experimental
Quellenangaben Volume: 172, Issue: , Pages: , Article Number: 156358 Supplement: ,
Publisher Elsevier
Publishing Place 1600 John F Kennedy Boulevard, Ste 1800, Philadelphia, Pa 19103-2899 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502600-008
G-502600-002
Grants ERC
(Saxon State Parliament)
DOI 10.1016/j.metabol.2025.156358
WOS ID 001547544500001
Scopus ID 105012447819
PubMed ID 40754155
Erfassungsdatum 2025-10-08
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