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Adipocyte and Cell Biology

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

International Journal of Obesity volume 49, pages 809–818 (2025)Cite this article

Subjects

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 patients with obesity but whether these changes initiate a fibro-inflammatory response at the tissue level remains insufficiently explored.

Objective

We investigated the markers of adipose tissue dysfunction (immune cell infiltration, secretion pattern and fibrosis) in tumor-free MAT of patients with obesity versus patients who are lean.

Methods

Tumor-free MAT were obtained from 96 women with (n = 43) or without (n = 53) obesity who underwent mastectomy for breast cancer risk reduction or treatment. Immune and non-immune cell infiltration were determined using flow cytometry. Bulk transcriptomic was used to characterize the phenotype of CD206+ macrophages whose infiltration is increased in patients with obesity. 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, 3D imaging of red picrosirius-stained tissues and measure of hydroxyproline content.

Results

We observed an increase of CD206+/HLA-DR+ macrophages in the stromal vascular fraction of MAT from patients with obesity compared to patients who are lean. 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 expression and processing in obesity. In addition, no heightened secretion of pro-inflammatory cytokines, TGF-β1 or MCP-1 was observed in the samples from patients with obesity. ECM characterization revealed an absence of fibrosis, with MAT of patients with obesity showing even a slightly reduced collagen secretion and deposition compared with their lean counterparts.

Conclusions

Obesity is not associated with inflammation nor fibrosis in MAT, highlighting its unique behavior.

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Fig. 1: Characterization of the stromal vascular fraction (SVF) of MAT from patients with or without obesity.
Fig. 2: Absence of increased secretion of pro-inflammatory cytokines by MAT from patients with obesity compared to those who are lean.
Fig. 3: Under-representation of ECM proteins in the conditioned medium of MAT from patients with obesity.
Fig. 4: Absence of fibrosis in MAT from patients with obesity.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work benefited from the Toulouse Réseau Imagerie (TRI)-RIO Optical Imaging Platform at the Institute of Pharmacology and Structural Biology (Genotoul, Toulouse, France). We thank Mathilde Lacombe (IPBS, Toulouse) for her writing assistance. We thank Jessica Tran for her contribution in the hydroxyproline quantification experiments.

Funding

This study was funded by the Ligue Contre le Cancer (Comité Midi-Pyrénées), and by the Institut National Contre le Cancer (Programme d’actions intégrées de recherche (PAIR)—Obésités et Cancers, INCa_18711). This study was funded in part by the French Ministry of Research with the Investissement d’Avenir Infrastructures Nationales en Biologie et Santé program (ProFI, Proteomics French Infrastructure project, ANR-10-INBS-08) (to OBS). LO received a master fellowship (Program “Espoirs de la recherche”) from the Fondation pour la Recherche Médicale (FRM). MR received a PhD fellowship from the Ligue Nationale contre le Cancer and from the Fondation pour la Recherche Médicale (FRM). CA received a master fellowship from the Association pour la Recherche sur le Cancer (ARC).

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Author notes

  1. These authors contributed equally: Anne Bouloumié, Charlotte Vaysse, Catherine Muller.

Authors and Affiliations

  1. Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, Université Toulouse III—Paul Sabatier (UT3), Toulouse, France

    Frédérique Fallone, Marie Rebeaud, Caroline Bouche, Carlo Arellano, Manuelle Ducoux-Petit, Lucyle Orgerit, Rémi Deudon, David Estève, Emmanuelle Mouton-Barbosa, Stéphanie Dauvillier, Mohamed Moutahir, Odile Burlet-Schiltz, Charlotte Vaysse & Catherine Muller

  2. Département de Chirurgie Gynécologique Oncologique, CHU-Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France

    Caroline Bouche, Carlo Arellano, Lucyle Orgerit, Rémi Deudon & Charlotte Vaysse

  3. Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse, INSERM, UPS, Toulouse, France

    Jessica Fontaine & Anne Bouloumié

  4. Infrastructure Nationale de Protéomique, ProFI, FR 2048, Toulouse, France

    Manuelle Ducoux-Petit, Emmanuelle Mouton-Barbosa & Odile Burlet-Schiltz

  5. Université Paris Cité, Centre de Recherche sur l’Inflammation (CRI), INSERM, U1149, CNRS, ERL 8252, F-75018, Paris, France

    Rémy Nicolle

  6. Département d’Anatomo-Pathologie, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France

    Camille Franchet

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  1. Frédérique Fallone
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Contributions

FF, MR and CB performed and analyzed most of the experiments presented in the manuscript and prepared the figures. SD and CA performed and prepared the figures of the imaging experiments (3D picrosirius staining). LO and RD performed the flow cytometry experiments with the help of JF under the supervision of AB. LO prepared the samples for proteomic analysis, FF, MDP and EMB performed the analysis of the proteomic data under the supervision of OBS. RN and FF performed the analysis of the RNA-seq. CF performed the Trichrome Masson staining which was analyzed by CV and DE. CA, CB and CV supervised the collection of human mammary adipose tissue samples and MM participated to tissue processing. AB, CV, FF, and CM supervised the study and wrote the manuscript. FF and MR performed the experiments required for the revision process. All the authors reviewed the manuscript. All the authors agreed with the final version of the manuscript.

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Correspondence to Frédérique Fallone or Catherine Muller.

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Fallone, F., Rebeaud, M., Bouche, C. et al. Lack of fibro-inflammatory response in human mammary adipose tissue in obesity. Int J Obes 49, 809–818 (2025). https://doi.org/10.1038/s41366-024-01705-1

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