多胺代谢在调节肥胖的脂肪组织稳态中的关键作用。

IF 11.9 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Metabolism: clinical and experimental Pub Date : 2025-11-01 Epub Date: 2025-08-05 DOI:10.1016/j.metabol.2025.156358
Christine Mund, Anupam Sinha, Anika Aderhold, Ivona Mateska, Eman Hagag, Sofia Traikov, Bettina Gercken, Andres Soto, Jonathan Pollock, Lilli Arndt, Michele Wölk, Natalie Werner, Georgia Fodelianaki, Pallavi Subramanian, Kyoung-Jin Chung, Sylvia Grossklaus, Mathias Langner, Mohamed Elgendy, Tatyana Grinenko, Ben Wielockx, Andreas Dahl, Martin Gericke, Matthias Blüher, Ünal Coskun, David Voehringer, Maria Fedorova, Mirko Peitzsch, Peter J Murray, Triantafyllos Chavakis, Vasileia Ismini Alexaki
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引用次数: 0

摘要

背景和目的:脂肪组织功能是系统代谢稳态的组成部分。脂肪组织的过度生长与慢性低度炎症和全身代谢障碍的发展有关。调节脂肪组织生长和体内平衡的细胞代谢途径尚不清楚。本文研究了多胺代谢在脂肪组织(病理)生理中的作用。方法:我们制造了全球和脂肪细胞祖细胞(AP)特异性抗酶抑制剂2 (AZIN2)缺乏的小鼠,并进行了饮食诱导的肥胖研究。从小鼠皮下和性腺脂肪组织中分离APs并进行培养。结果:多胺代谢成分AZIN2在APs中高表达,其在脂肪组织中的表达随肥胖而下调。IL4诱导APs中Azin2的表达。AZIN2促进多胺合成和乙酰化,并调节APs中总乙酰辅酶a水平。AZIN2缺乏上调脂质代谢相关基因的组蛋白乙酰化。与野生型相比,Azin2-/- APs在体内和体外更有效地进行脂肪形成,更容易衰老。在饮食引起的肥胖中,小鼠整体和AP特异性AZIN2缺乏引起AP消耗、脂肪细胞肥大、肥胖、炎症、葡萄糖耐受不良和胰岛素抵抗。在人脂肪组织中,AZIN2的表达与祖细胞标志物的表达密切相关。结论:总之,我们发现AZIN2是一种新的AP标记物,可以调节AP的命运并保持脂肪组织的健康。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A key role of polyamine metabolism in adipose tissue homeostasis that regulates obesity.

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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来源期刊
Metabolism: clinical and experimental
Metabolism: clinical and experimental 医学-内分泌学与代谢
CiteScore
18.90
自引率
3.10%
发文量
310
审稿时长
16 days
期刊介绍: Metabolism upholds research excellence by disseminating high-quality original research, reviews, editorials, and commentaries covering all facets of human metabolism. Consideration for publication in Metabolism extends to studies in humans, animal, and cellular models, with a particular emphasis on work demonstrating strong translational potential. The journal addresses a range of topics, including: - Energy Expenditure and Obesity - Metabolic Syndrome, Prediabetes, and Diabetes - Nutrition, Exercise, and the Environment - Genetics and Genomics, Proteomics, and Metabolomics - Carbohydrate, Lipid, and Protein Metabolism - Endocrinology and Hypertension - Mineral and Bone Metabolism - Cardiovascular Diseases and Malignancies - Inflammation in metabolism and immunometabolism
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