Adhesion-Related Macrophages Regulates Metabolic Homeostasis through CAV-1 Dependency

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). We developed an approach to isolate ARMs and compared them with traditional macrophages from the stromal vascular fraction. Our findings demonstrate that ARMs constitute the predominant expanded subpopulation of adipose tissue macrophages 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. Our studies uncover 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.