Combined pharmacological targeting of CD9+ progenitors alleviates obesity-induced adipose tissue fibrosis and metabolic impairment
Fibrosis in visceral white adipose tissue (vWAT) is closely associated with tissue dysfunction and systemic metabolic disturbances in obesity. Identifying pathways amenable to drug intervention to prevent fibrotic changes in vWAT is a critical step in addressing the array of metabolic complications associated with obesity. CD9<sup>+</sup> adipose progenitors (Progs) are key drivers of vWAT fibrosis. Here, we explore pharmacological strategies to target these cells and improve metabolic health. Profiling of CD9<sup>+</sup> Progs reveals pro-fibrotic pathways that can be targeted by the Food and Drug Administration (FDA)-approved drugs nintedanib and celecoxib. Treatment with this combination blocks the progression of vWAT fibrosis and improves systemic metabolism in obese mice. Within the CD9<sup>+</sup> Prog population, both Ly-6C<sup>+</sup> Progs and mesothelial cells adopt a pro-fibrotic phenotype during obesity, a shift markedly reduced by the drug treatment. Our data highlight the importance of targeting adipose progenitors to counteract fibrosis and preserve adipose tissue function.
Authors
- Jaqueline Pereira (ORCID: https://orcid.org/0009-0003-8909-4188)
- Emmanuel L. Gautier (ORCID: https://orcid.org/0000-0003-2976-7566)
- Sébastien Dussaud (ORCID: https://orcid.org/0000-0002-5365-8338)
- Jean-Christophe Bichet
- Laurent Genser (ORCID: https://orcid.org/0000-0001-7635-7813)
- Gabriela Barbosa Pires Fagundes (ORCID: https://orcid.org/0000-0003-3654-0140)
- Karine Clément (ORCID: https://orcid.org/0000-0002-2489-3355)
- Geneviève Marcelin (ORCID: https://orcid.org/0000-0002-9779-5529)
- Alexandre Boissonnas (ORCID: https://orcid.org/0000-0002-7770-7210)
- Cindy Rose (ORCID: https://orcid.org/0009-0003-6350-6308)
- Adaliene Versiani Matos Ferreira (ORCID: https://orcid.org/0000-0003-2256-8652)
- Simon Lecoutre (ORCID: https://orcid.org/0000-0002-2536-6119)
- Véronique Pelloux (ORCID: https://orcid.org/0000-0003-3630-4746)
- Solia Adriouch (ORCID: https://orcid.org/0000-0002-7372-4398)
- Fatiha Merabtene
- Christine Poitou (ORCID: https://orcid.org/0000-0001-7769-6331)
- Ana Letícia Malheiros Silveira (ORCID: https://orcid.org/0000-0003-1052-0854)
- François Lanthiez (ORCID: https://orcid.org/0009-0008-8135-6493)
- Clémentine Rebière (ORCID: https://orcid.org/0009-0009-2816-6997)
- Jimon Boniface Abatan
- Jean Debédat (ORCID: https://orcid.org/0000-0002-8377-5965)
- Judith Aron‐Wisnewsky
- A. C. Oliveira (ORCID: https://orcid.org/0009-0007-5205-1730)
- Christine Rouault
Institutions
- Universidade Federal de Minas Gerais (BR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Sorbonne Université (FR)
- Nutrition et obésité : approches systémiques (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Centre d'Immunologie et des Maladies Infectieuses (FR)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-06-18
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102197
- Primary Topic
- Adipokines, Inflammation, and Metabolic Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00