Lack of fibro-inflammatory response in human mammary adipose tissue in obesity

ABSTRACT: Background Understanding how obesity impacts human mammary adipose tissue (MAT) biology is crucial for deciphering its role in mammary epithelium during both physiological and pathophysiological processes, including breast cancer. Hypertrophic mammary adipocytes and Crown-like Structures are present in MAT of obese patients but whether these changes initiate a fibro-inflammatory response at the tissue level remains insufficiently explored. Objective We aimed to investigate the markers of adipose tissue dysfunction (immune cell infiltration, secretion pattern and fibrosis) in tumor-free MAT of obese versus lean patients Methods Tumor-free MAT were obtained from 61 lean and obese women who underwent mastectomy for breast cancer risk reduction or treatment. Immune and non-immune cell infiltration was determined using flow cytometry. Bulk transcriptomic was used to characterize the phenotype of CD206+ macrophages whose infiltration is increased in obese. Conditioned-medium were prepared from MAT to characterize their secretome and dose adipokines and cytokines by ELISA assay. The extra-cellular matrix (ECM) deposition was evaluated by Masson trichrome staining on cross-stained sections and 3D imaging of red picrosirius-stained tissues. Results We observed an increase in CD206+/HLA-DR+ macrophages in the stromal vascular fraction of MAT from obese patients compared to lean ones. Other immune cell infiltration and endothelial or adipose progenitor cell numbers were similar between groups. Bulk transcriptomics on CD206+ macrophages revealed a significant decrease in ECM component secretion and processing in obese samples. Additionally, no heightened secretion of pro-inflammatory cytokines or MCP-1 was noted in obese samples. ECM characterization indicated an absence of fibrosis, with obese MAT showing reduced collagen secretion and deposition compared to lean counterparts. Conclusions Obesity does not associate with inflammation or fibrosis in MAT, underscoring its unique behavior.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Fat Cell

SUBMITTER: Manuelle Ducoux-Petit  

LAB HEAD: Odile Schiltz

PROVIDER: PXD050896 | Pride | 2025-01-07

REPOSITORIES: pride