Fibrocytes enhance mammary gland fibrosis in obesity

Obesity rates continue to rise, and obese individuals are at higher risk for multiple types of cancer, including breast cancer. Obese mammary fat is a site of chronic, macrophage-driven inflammation, which enhances fibrosis within adipose tissue. Elevated fibrosis within the mammary gland may contribute to risk for obesity-associated breast cancer. To understand how inflammation due to obesity enhanced fibrosis within mammary tissue, we utilized a high-fat diet model of obesity and elimination of CCR2 signaling in mice to identify changes in immune cell populations and their impact on fibrosis. We observed that obesity increased a population of CD11b(+) cells with the ability to form myofibroblast-like colonies in vitro. This population of CD11b(+) cells is consistent with fibrocytes, which have been identified in wound healing and chronic inflammatory diseases but have not been examined in obesity. In CCR2-null mice, which have limited ability to recruit myeloid lineage cells into obese adipose tissue, we observed reduced mammary fibrosis and diminished fibrocyte colony formation in vitro. Transplantation of myeloid progenitor cells, which are the cells of origin for fibrocytes, into the mammary glands of obese CCR2-null mice resulted in significantly increased myofibroblast formation. Gene expression analyses of the myeloid progenitor cell population from obese mice demonstrated enrichment for genes associated with collagen biosynthesis and extracellular matrix remodeling. Together these results show that obesity enhances recruitment of fibrocytes to promote obesity-induced fibrosis in the mammary gland.

Automated summary

Obesity increases the risk of breast cancer, and this is partly due to chronic inflammation and fibrosis in the mammary gland. In this study, the researchers used a high-fat diet model and genetically modified mice to investigate the role of immune cells in obesity-induced fibrosis. They found that obesity increased the recruitment of a specific population of cells, called fibrocytes, which contributed to the formation of myofibroblasts and fibrosis in the mammary gland. Transplanting myeloid progenitor cells, which give rise to fibrocytes, into obese mice further increased myofibroblast formation. These findings suggest that obesity enhances the recruitment of fibrocytes and promotes fibrosis in the mammary gland.