205-OR: Adhesion-Related Macrophages Regulates Metabolic Homeostasis through Cav-1 Dependency

Introduction and Objective: The significance of adipose tissue macrophages (ATMs) in regulating adipose tissue function is well-established. However, our investigation revealed a previously overlooked subpopulation of macrophages adhered to adipocytes, which we term adhesion-related macrophages (ARMs). Methods: We developed a method to isolate both ARMs and non-ARMs. Molecular and functional differences were analyzed, and Cav-1 knockout mice were utilized to study the role of ARMs in metabolism. Results: Our findings demonstrate that ARMs constitute the predominant expanded subpopulation of ATMs during obesity, exhibiting heightened adhesion, proliferation, and lipid-processing capacities. Notably, ARMs can be characterized by a key functional marker, Caveolin-1. Genetic ablation of Caveolin-1 in immune cells significantly diminishes ARM abundance, disrupting their adhesion capacity and lipid content, leading to adipocyte hypertrophy, adipose tissue expansion, and impaired glucose homeostasis. Reintroducing ARMs from lean mice into eWAT mitigate obesity-induced adipose tissue inflammation and insulin resistance. Conclusion: Our study uncovers a previously unexplored macrophage subpopulation, ARMs, revealing potential therapeutic targets for obesity-induced insulin resistance and opening avenues for identifying similar paradigms in other tissues and diseases. Disclosure W. Hu: None. T. Deng: None. Funding National Key R&D Program of China (2020YFA0803604 and 2023YFC3603404), the Key Program of the National Natural Science Foundation of China (82130024), the Fund for International Cooperation and Exchange of the National Natural Science Foundation of China (8231101033).