PT  - JOURNAL ARTICLE
AU  - Nabil Rabhi
AU  - Kathleen Desevin
AU  - Anna C Belkina
AU  - Andrew Tilston-Lunel
AU  - Xaralabos Varelas
AU  - Matthew D Layne
AU  - Stephen R Farmer
TI  - Obesity-induced senescent macrophages activate a fibrotic transcriptional program in adipocyte progenitors
AID  - 10.26508/lsa.202101286
DP  - 2022 May 01
TA  - Life Science Alliance
PG  - e202101286
VI  - 5
IP  - 5
4099  - https://www.life-science-alliance.org/content/5/5/e202101286.short
4100  - https://www.life-science-alliance.org/content/5/5/e202101286.full
SO  - Life Sci. Alliance2022 May 01; 5
AB  - Adipose tissue fibrosis is regulated by the chronic and progressive metabolic imbalance caused by differences in caloric intake and energy expenditure. By exploring the cellular heterogeneity within fibrotic adipose tissue, we demonstrate that early adipocyte progenitor cells expressing both platelet-derived growth factor receptor (PDGFR) α and β are the major contributors to extracellular matrix deposition. We show that the fibrotic program is promoted by senescent macrophages. These macrophages were enriched in the fibrotic stroma and exhibit a distinct expression profile. Furthermore, we demonstrate that these cells display a blunted phagocytotic capacity and acquire a senescence-associated secretory phenotype. Finally, we determined that osteopontin, which was expressed by senescent macrophages in the fibrotic environment promoted progenitor cell proliferation, fibrotic gene expression, and inhibited adipogenesis. Our work reveals that obesity promotes macrophage senescence and provides a conceptual framework for the discovery of rational therapeutic targets for metabolic and inflammatory disease associated with obesity.