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 language | English (US) |
|---|---|
| Pages (from-to) | 673-685 |
| Number of pages | 13 |
| Journal | Cell Metabolism |
| Volume | 25 |
| Issue number | 3 |
| DOIs | |
| State | Published - 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
A PDGFRα-Mediated Switch toward CD9high Adipocyte Progenitors Controls Obesity-Induced Adipose Tissue Fibrosis. / Marcelin, Geneviève; Ferreira, Adaliene; Liu, Yuejun; Atlan, Michael; Aron-Wisnewsky, Judith; Pelloux, Véronique; Botbol, Yair M.; Ambrosini, Marc; Fradet, Magali; Rouault, Christine; Hénégar, Corneliu; Hulot, Jean Sébastien; Poitou, Christine; Torcivia, Adriana; Nail-Barthelemy, Raphael; Bichet, Jean Christophe; Gautier, Emmanuel L.; Clément, Karine.
In: Cell Metabolism, Vol. 25, No. 3, 07.03.2017, p. 673-685.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A PDGFRα-Mediated Switch toward CD9high Adipocyte Progenitors Controls Obesity-Induced Adipose Tissue Fibrosis
AU - Marcelin, Geneviève
AU - Ferreira, Adaliene
AU - Liu, Yuejun
AU - Atlan, Michael
AU - Aron-Wisnewsky, Judith
AU - Pelloux, Véronique
AU - Botbol, Yair M.
AU - Ambrosini, Marc
AU - Fradet, Magali
AU - Rouault, Christine
AU - Hénégar, Corneliu
AU - Hulot, Jean Sébastien
AU - Poitou, Christine
AU - Torcivia, Adriana
AU - Nail-Barthelemy, Raphael
AU - Bichet, Jean Christophe
AU - Gautier, Emmanuel L.
AU - Clément, Karine
PY - 2017/3/7
Y1 - 2017/3/7
N2 - 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.
AB - 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.
KW - adipose tissue
KW - fibrosis
KW - insulin resistance
KW - obesity
KW - progenitors
UR - http://www.scopus.com/inward/record.url?scp=85012896702&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85012896702&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2017.01.010
DO - 10.1016/j.cmet.2017.01.010
M3 - Article
C2 - 28215843
AN - SCOPUS:85012896702
VL - 25
SP - 673
EP - 685
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 3
ER -