A PDGFRα-Mediated switch toward CD9ʰᶦᵍʰ adipocyte progenitors controls obesity-induced adipose tissue fibrosis

Descrição

Tipo

Artigo de periódico

Título alternativo

Primeiro orientador

Membros da banca

Resumo

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-a-positive (PDGFRa+) progenitors adopt a fibrogenic phenotype in obese mice prone to visceral WAT fibrosis. More specifically, a subset of PDGFRa+ 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. PDGFRa pathway activation promotes a phenotypic shift toward PDGFRa+ 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 PDGFRa+ cell subsets modulate obesity-induced WAT fibrogenesis and are associated with loss of metabolic fitness.

Abstract

Assunto

Tecido adiposo branco, Obesidade, Fibrose

Palavras-chave

White adipose tissue, Obesity, Fibrosis

Citação

Curso

Endereço externo

https://www.sciencedirect.com/science/article/pii/S1550413117300451?via%3Dihub

Avaliação

Revisão

Suplementado Por

Referenciado Por