# CD9 regulates macrophage-mediated remodeling of adipose tissue in obesity

## TL;DR

CD9 helps macrophages in fat tissue cause harmful changes during obesity, and removing CD9 improves metabolism and reduces tissue damage.

## Contribution

This study identifies CD9 as a causal regulator of pathogenic macrophage functions in obesity.

## Key findings

- CD9 supports macrophage-adipocyte adhesion and crown-like structure formation.
- Deleting CD9 reduces adipose tissue fibrosis and improves metabolic outcomes in obesity.
- CD9 promotes profibrotic and extracellular matrix remodeling gene expression.

## Abstract

Dysfunctional white adipose tissue contributes to the development of obesity-related morbidities, including insulin resistance, dyslipidemia, and other metabolic disorders. Adipose tissue macrophages (ATMs) accumulate in obesity and play both beneficial and harmful roles in the maintenance of adipose tissue homeostasis and function. Despite their importance, the molecules and mechanisms that regulate these diverse functions are not well understood. Lipid-associated macrophages (LAMs), the dominant subset of obesity-associated ATMs, accumulate in crown-like structures and are characterized by a metabolically activated and proinflammatory phenotype. We previously identified CD9 as a surface marker of LAMs. However, the contribution of CD9 to the activation and function of LAMs during obesity is unknown. Using a myeloid-specific CD9-KO model, we show that CD9 supports ATM-adipocyte adhesion and crown-like structure formation. Furthermore, CD9 promotes the expression of profibrotic and extracellular matrix remodeling genes. Loss of myeloid CD9 reduces adipose tissue fibrosis, increases visceral adipose tissue accumulation, and improves global metabolic outcomes during diet-induced obesity. These results identify CD9 as a causal regulator of pathogenic LAM functions, highlighting CD9 as a potential therapeutic target for treating obesity-associated metabolic disease.

CD9 regulates adipose tissue macrophage adhesion and pro-fibrotic activation. Deleting CD9 improves adipose tissue fibrosis and global metabolism during obesity, identifying it as a potential therapeutic target.