Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière Hospital, F-75013 Paris, France; INSERM, UMRS 1166 (teams 2, 4, and 6 NutriOmics), F-75013 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMRS 1166, F-75013 Paris, France.
Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière Hospital, F-75013 Paris, France; INSERM, UMRS 1166 (teams 2, 4, and 6 NutriOmics), F-75013 Paris, France; Immunometabolism, Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil.
Cell Metab. 2017 Mar 7;25(3):673-685. doi: 10.1016/j.cmet.2017.01.010. Epub 2017 Feb 16.
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 (CD9) originates pro-fibrotic cells whereas their CD9 counterparts, committed to adipogenesis, are almost completely lost in the fibrotic WAT. PDGFRα pathway activation promotes a phenotypic shift toward PDGFRαCD9 fibrogenic cells, driving pathological remodeling and altering WAT function in obesity. These findings translated to human obesity as the frequency of CD9 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.
肥胖引起的白色脂肪组织（WAT）纤维化被认为会加速 WAT 功能障碍。然而，WAT 纤维化的细胞来源仍不清楚。在这里，我们表明，肥胖小鼠中易发生内脏 WAT 纤维化的脂肪细胞血小板衍生生长因子受体-α阳性（PDGFRα）祖细胞表现出纤维生成表型。更具体地说，具有高 CD9 表达（CD9）的 PDGFRα 细胞亚群起源于促纤维化细胞，而其向脂肪生成分化的 CD9 对应物在纤维化的 WAT 中几乎完全丢失。PDGFRα 途径的激活促进了向 PDGFRαCD9 纤维生成细胞的表型转变，导致肥胖中的病理性重塑和改变 WAT 功能。这些发现与人类肥胖相关，因为网膜 WAT（oWAT）中的 CD9 祖细胞的频率与 oWAT 纤维化程度、胰岛素抵抗严重程度和 2 型糖尿病相关。总的来说，我们的数据表明，除了代表 WAT 成脂龛外，不同的 PDGFRα 细胞亚群还调节肥胖诱导的 WAT 纤维化，并与代谢适应性丧失相关。
