肥胖时，白色脂肪组织需要对细胞外基质进行重建以适应脂肪细胞肥大、新脂肪细胞形成、炎症细胞浸润、新生血管形成等变化。一直以来，人们忽略了细胞外基质作为重要细胞外微环境对脂肪细胞发育的作用。ADAMTS1是一种新型基质金属蛋白酶，对细胞外基质重建非常重要。研究表明ADAMTS1在肥胖小鼠皮下脂肪组织表达下降，但具体机制还不清楚。本项目首次发现在多潜能干细胞向前脂肪细胞定向过程中ADAMTS1表达明显降低，同时伴有细胞外基质组成改变。这些结果提示ADAMTS1可能通过影响细胞外微环境来调节脂肪细胞定向。因此我们希望利用已经建立的多潜能干细胞向脂肪细胞定向分化的细胞模型、BMP4转基因小鼠和高脂饮食诱导的肥胖小鼠模型来阐明ADAMTS1如何通过影响细胞外微环境调节多潜能干细胞向前脂肪细胞定向。该研究将为确定脂肪细胞定向过程中的关键因子及探寻通过改变细胞微环境作为防治肥胖及相关代谢性疾病提供新思路。

Development of obesity is associated with modulation of adipose tissue structure, involving adipogenesis, angiogenesis, and extracellular matrix （ECM）remodelling. In adipose tissue, the ECM is crucial for maintaining the structural integrity of adipocytes and plays a pivotal role in adipogenesis and whole tissue formation. Formation of adipose tissue is a complex process requiring designation of mesodermal stem cells to a preadipocyte lineage and differentiation of preadipocytes into adipocytes. However, the origin and potential impact of ECM in adipocyte lineage commitment are still unclear.Our previous studies showed that ADAMTS1(a new metalloprotease) decreased during the commitment of mesenchymal stem cells (MSCs)to adipocytic lineage. This is in line with the study repoted by other group that the expression of ADAMTS1 reduced in subcutaneous adipose tissue of obese mice.Our further studies showed that many ECM components also changed during adipocyte lineage commitment.Considering the metalloprotease activity of ADAMTS1,we proposed that ADAMTS1 may contribute to the commitment of preadipocyte by remodelling microenvironment. In this study, we are going to explore the contribution of ADAMTS1 to the microenvironment of MSCs and subsequent commitment to adipocyte lineage both in vivo and in vitro,and how ADAMTS1 is regulated during adipocyte commitment are also involed in the this study. Our studies will open up new opportunities for the development of drugs for obesity and its metabolic and cardiovascular complications.