Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, China.
Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nat Commun. 2024 Jun 6;15(1):4827. doi: 10.1038/s41467-024-48914-w.
Adipose progenitor cells (APCs) are heterogeneous stromal cells and help to maintain metabolic homeostasis. However, the influence of obesity on human APC heterogeneity and the role of APC subpopulations on regulating glucose homeostasis remain unknown. Here, we find that APCs in human visceral adipose tissue contain four subsets. The composition and functionality of APCs are altered in patients with type 2 diabetes (T2D). CD9CD55 APCs are the subset which is significantly increased in T2D patients. Transplantation of these cells from T2D patients into adipose tissue causes glycemic disturbance. Mechanistically, CD9CD55 APCs promote T2D development through producing bioactive proteins to form a detrimental niche, leading to upregulation of adipocyte lipolysis. Depletion of pathogenic APCs by inducing intracellular diphtheria toxin A expression or using a hunter-killer peptide improves obesity-related glycemic disturbance. Collectively, our data provide deeper insights in human APC functionality and highlights APCs as a potential therapeutic target to combat T2D. All mice utilized in this study are male.
脂肪祖细胞 (APCs) 是异质性的基质细胞，有助于维持代谢稳态。然而，肥胖对人类 APC 异质性的影响以及 APC 亚群在调节葡萄糖稳态中的作用尚不清楚。在这里，我们发现人类内脏脂肪组织中的 APC 包含四个亚群。2 型糖尿病 (T2D) 患者的 APC 组成和功能发生改变。CD9CD55 APC 是在 T2D 患者中显著增加的亚群。将这些细胞从 T2D 患者移植到脂肪组织中会导致血糖紊乱。在机制上，CD9CD55 APC 通过产生生物活性蛋白形成有害的龛位来促进 T2D 的发展，导致脂肪细胞脂解的上调。通过诱导细胞内白喉毒素 A 表达或使用猎人-杀手肽耗竭致病 APC 可改善肥胖相关的血糖紊乱。总的来说，我们的数据提供了对人类 APC 功能的更深入了解，并强调 APC 是对抗 T2D 的潜在治疗靶点。本研究中使用的所有小鼠均为雄性。
