2025
Metabolism. 2025 Nov:172:156358. doi: 10.1016/j.metabol.2025.156358. Epub 2025 Aug 5.
A key role of polyamine metabolism in adipose tissue homeostasis that regulates obesity
Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. Department of Infection Biology, Universitätsklinikum Erlangen and Friedrich-Alexander, University Erlangen-Nürnberg, Erlangen, Germany. Institute of Anatomy, Leipzig University, Leipzig, Germany. Center of Membrane Biochemistry and Lipid Research, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany. DRESDEN-concept Genome Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany. Clinic and Policlinic for Endocrinology and Nephrology, Medical Research Center, Universitätsmedizin Leipzig, Germany. Center of Membrane Biochemistry and Lipid Research, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden of the Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany. Max Planck Institute of Biochemistry, Martinsried, Germany. Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden of the Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany. Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Service type: Knock-in mice
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.
Keywords: AZIN2; Adipocyte progenitors; Adipose tissue; Obesity; Polyamine metabolism.
