BMP9通过抑制白色脂肪分化和调节脂质代谢调控全身能量代谢

骨代谢和能量代谢之间存在密切“对话”，尤其骨可以分泌骨源性因子调控自身代谢和能量代谢。所以，探索调控骨代谢和能量代谢的新型骨源性因子，将有助于明确骨质疏松、肥胖和糖尿病的共同治疗靶点，为这些疾病的共同防治提供新的方向。本课题组前研究发现新骨源性因子BMP9通过调控骨重建改善OVX小鼠骨表型。本课题组前期工作初步发现BMP9高表达可以降低肥胖小鼠的体脂分数、脂肪组织的重量和体积，并抑制脂肪分化指标；体外实验也初步证实，还发现BMP9可以抑制脂质合成及激活Wnt信号通路，因此我们推测BMP9可能通过增强Wnt信号通路，抑制白色脂肪分化和调节脂质代谢，进而调控全身能量代谢。我们将利用AAV高表达技术、APALK1小鼠模型、ob/ob小鼠、慢病毒干扰等，研究BMP9对能量代谢的影响，并探讨BMP9调控能量代谢的内在机制，发现骨质疏松、肥胖和糖尿病共同治疗靶点，并为这些疾病的共同防治提供理论依据。

There is a close "dialogue" between bone metabolism and energy metabolism. In particular, bone has been proven to be an endocrine organ that regulates energy metabolism. Bone regulates its own metabolism and energy metabolism by secreting bone-derived factors. New bone-derived factors that regulate bone metabolism and energy metabolism will help clarify the common therapeutic targets for osteoporosis, obesity and diabetes, and provide new ideas for the common prevention and treatment of these diseases. Previous research by our group found that the new bone-derived factor BMP9 improves osteoporosis phenotype of OVX mice by regulating bone remodeling and reduces the weight of OVX mice. Our team's previous work initially found that BMP9 overexpression could reduce the body fat and the weight and volume of adipose tissue in obese mice, and inhibited the white fat differentiation. In vitro experiments have also confirmed this results，and also found BMP9 could inhibit lipid synthesis and activate Wnt signaling. Therefore, we speculated that BMP9 may regulate energy metabolism by inhibiting adipocyte differentiation and regulating lipid metabolism. We will study the effect of BMP9 on energy metabolism and explore its mechanisms by using AAV overexpression, APALK1 mouse models, ob/ob mice, lentiviral interference and so on. This project will discover common therapeutic targets for osteoporosis, obesity and diabetes, and provide a theoretical basis for the common prevention and treatment of these diseases.