Publication date: Available online 16 February 2017
Source:Cell Metabolism
Author(s): Geneviève Marcelin, Adaliene Ferreira, Yuejun Liu, Michael Atlan, Judith Aron-Wisnewsky, Véronique Pelloux, Yair 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
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.
Graphical abstract
Teaser
In obese subjects, white adipose tissue (WAT) fibrosis represents a maladaptive mechanism contributing to the loss of metabolic fitness and obesity-associated comorbidities. Marcelin et al. demonstrate that elevated PDGFRα+ progenitor subsets with high CD9 expression promote WAT fibrosis and are associated with metabolic deteriorations in mice and humans.http://ift.tt/2lq9ZS4
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