Adhesion‐Related Macrophages Regulate 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 stromal vascular fraction (SVF) macrophages (SMs). Our findings demonstrate that ARMs constitute the predominant expanded subpopulation of ATMs during obesity, ARMs acquire adipocyte mRNA through direct adhesion to adipocytes, thereby enhancing their lipid processing capacity. Notably, ARMs can be characterized by a key functional marker, Caveolin-1. Genetic ablation of Caveolin-1 in macrophages 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 epididymal white adipose tissue (eWAT) mitigates obesity-induced insulin resistance. Our study uncovers ARM as a potential therapeutic target for obesity-induced insulin resistance and opening avenues for identifying similar paradigms in other tissues and diseases.

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Publication Details

Journal
Advanced Science
Published
2026-03-12
DOI
https://doi.org/10.1002/advs.202520936
Primary Topic
Caveolin-1 and cellular processes
Type
article
Field-Weighted Citation Impact
0.00
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article

Adhesion‐Related Macrophages Regulate Metabolic Homeostasis Through CAV‐1 Dependency

Xiyan Liao, Fanqi Wang, J. C. Liu, Willa A. Hsueh et al.
Advanced Science
Caveolin-1 and cellular processes
article

Adhesion‐Related Macrophages Regulate Metabolic Homeostasis Through CAV‐1 Dependency

Xiyan Liao, Fanqi Wang, J. C. Liu, Willa A. Hsueh, Xiaoxiao Sun, Hong Jiang, Wufuer Aini, Limin Xie, Weijie Liu, Qin Zeng, Tuo Deng, Wanqin Xie, Yiyu Cheng, Helong Dai, Jianfeng Song, Ying Mei, Lei Li, Hui Zhou, Dandan Wang, Wanyu Hu, Yujin Din, Haowei Zhang, Feng Liu, Luodi Jing
article en

Abstract

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 stromal vascular fraction (SVF) macrophages (SMs). Our findings demonstrate that ARMs constitute the predominant expanded subpopulation of ATMs during obesity, ARMs acquire adipocyte mRNA through direct adhesion to adipocytes, thereby enhancing their lipid processing capacity. Notably, ARMs can be characterized by a key functional marker, Caveolin-1. Genetic ablation of Caveolin-1 in macrophages 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 epididymal white adipose tissue (eWAT) mitigates obesity-induced insulin resistance. Our study uncovers ARM as a potential therapeutic target for obesity-induced insulin resistance and opening avenues for identifying similar paradigms in other tissues and diseases.

Advanced Science
Central South University (CN), Sun Yat-sen University (CN), The Ohio State University Wexner Medical Center (US), Sun Yat-sen Memorial Hospital (CN), First Affiliated Hospital of Henan University of Science and Technology (CN), First Affiliated Hospital of University of South China (CN), Second Xiangya Hospital of Central South University (CN), Department of Science and Technology of Hunan Province (CN), First Affiliated Hospital of Zhengzhou University (CN), Hunan Provincial Maternal and Child Health Hospital (CN), University of South China (CN)
Openalex Percentile: Top 26%
Caveolin-1 and cellular processes
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