A PDGFRα-Mediated Switch toward CD9high Adipocyte Progenitors Controls Obesity-Induced Adipose Tissue Fibrosis

Geneviève Marcelin, Adaliene Ferreira, Yuejun Liu, Michael Atlan, Judith Aron-Wisnewsky, Véronique Pelloux, Yair M. Botbol, Marc Ambrosini, Magali Fradet, Christine Rouault, Corneliu Hénégar, Jean Sébastien Hulot, Christine Poitou, Adriana Torcivia, Raphael Nail-Barthelemy, Jean Christophe Bichet, Emmanuel L. Gautier, Karine Clément

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Obesity-induced white adipose tissue (WAT) fibrosis is believed to accelerate WAT dysfunction. However, the cellular origin of WAT fibrosis remains unclear. Here, we show that adipocyte platelet-derived growth factor receptor-α-positive (PDGFRα+) progenitors adopt a fibrogenic phenotype in obese mice prone to visceral WAT fibrosis. More specifically, a subset of PDGFRα+ cells with high CD9 expression (CD9high) originates pro-fibrotic cells whereas their CD9low counterparts, committed to adipogenesis, are almost completely lost in the fibrotic WAT. PDGFRα pathway activation promotes a phenotypic shift toward PDGFRα+CD9high fibrogenic cells, driving pathological remodeling and altering WAT function in obesity. These findings translated to human obesity as the frequency of CD9high progenitors in omental WAT (oWAT) correlates with oWAT fibrosis level, insulin-resistance severity, and type 2 diabetes. Collectively, our data demonstrate that in addition to representing a WAT adipogenic niche, different PDGFRα+ cell subsets modulate obesity-induced WAT fibrogenesis and are associated with loss of metabolic fitness.

Original languageEnglish (US)
Pages (from-to)673-685
Number of pages13
JournalCell Metabolism
Volume25
Issue number3
DOIs
StatePublished - Mar 7 2017

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Keywords

  • adipose tissue
  • fibrosis
  • insulin resistance
  • obesity
  • progenitors

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Marcelin, G., Ferreira, A., Liu, Y., Atlan, M., Aron-Wisnewsky, J., Pelloux, V., Botbol, Y. M., Ambrosini, M., Fradet, M., Rouault, C., Hénégar, C., Hulot, J. S., Poitou, C., Torcivia, A., Nail-Barthelemy, R., Bichet, J. C., Gautier, E. L., & Clément, K. (2017). A PDGFRα-Mediated Switch toward CD9high Adipocyte Progenitors Controls Obesity-Induced Adipose Tissue Fibrosis. Cell Metabolism, 25(3), 673-685. https://doi.org/10.1016/j.cmet.2017.01.010