Luche Elodie, Robert Virginie, Cuminetti Vincent, Pomié Celine, Sastourné-Arrey Quentin, Waget Aurélie, Arnaud Emmanuelle, Varin Audrey, Labit Elodie, Laharrague Patrick, Burcelin Remy, Casteilla Louis, Cousin Beatrice
STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm U1031, UPS, Toulouse, France.
INSERM U1048, Université de Toulouse, EFS, INP-ENVT, Inserm U1031, UPS, Toulouse, France.
Elife. 2017 Jun 28;6:e23194. doi: 10.7554/eLife.23194.
Activation and increased numbers of inflammatory macrophages, in adipose tissue (AT) are deleterious in metabolic diseases. Up to now, AT macrophages (ATM) accumulation was considered to be due to blood infiltration or local proliferation, although the presence of resident hematopoietic stem/progenitor cells (Lin-/Sca+/c-Kit+; LSK phenotype) in the AT (AT-LSK) has been reported. By using transplantation of sorted AT-LSK and gain and loss of function studies we show that some of the inflammatory ATM inducing metabolic disease, originate from resident AT-LSK. Transplantation of AT-LSK sorted from high fat diet-fed (HFD) mice is sufficient to induce ATM accumulation, and to transfer metabolic disease in control mice. Conversely, the transplantation of control AT-LSK improves both AT-inflammation and glucose homeostasis in HFD mice. Our results clearly demonstrate that resident AT-LSK are one of the key point of metabolic disease, and could thus constitute a new promising therapeutic target to fight against metabolic disease.
脂肪组织（AT）中炎性巨噬细胞的激活及其数量增加在代谢性疾病中是有害的。到目前为止，尽管已有报道称脂肪组织中存在常驻造血干细胞/祖细胞（Lin-/Sca+/c-Kit+；LSK表型），但脂肪组织巨噬细胞（ATM）的积累一直被认为是由于血液浸润或局部增殖所致。通过使用分选的脂肪组织LSK进行移植以及功能获得和丧失研究，我们发现一些诱发代谢性疾病的炎性ATM起源于常驻脂肪组织LSK。从高脂饮食喂养（HFD）小鼠中分选的脂肪组织LSK移植足以诱导ATM积累，并将代谢性疾病转移至对照小鼠。相反，对照脂肪组织LSK的移植改善了HFD小鼠的脂肪组织炎症和葡萄糖稳态。我们的结果清楚地表明，常驻脂肪组织LSK是代谢性疾病的关键因素之一，因此可能构成对抗代谢性疾病的一个新的有前景的治疗靶点。
