肥胖、骨质疏松是最常见的内分泌代谢病。本课题组既往工作表明骨代谢、脂代谢和中枢神经系统间有密切的相互影响和调节。寻找来自于骨并能调节全身能量代谢的分子和/或信号通路是目前最前沿的研究核心。TGF-β超家族对骨的生长发育和维持有重要作用，同时参与能量代谢，mTOR信号则对能量代谢有调控作用。本课题将利用已有的成骨细胞部分性消除小鼠，并通过建立多种下丘脑和棕色脂肪细胞条件性敲除小鼠模型，在下丘脑、脂肪组织和骨组织几个层面，全面研究TGF-β超家族成员BMP7通过mTOR信号途径，对全身食欲、棕色脂肪产热的内分泌调控及其作用机制，阐明肥胖和骨量丢失的共同发病机制和治疗靶标，为今后研发针对调节食欲、骨密度的药物提供坚实的理论依据。

Obesity,and osteoporosis are the most common endocrine and metabolic diseases. Our previous works pointed to a deep involvement of bone in lipid metabolism and central nervous system. The bone is now widely accepted as an endocrine organ, however, the mechanism for the regulatory effect of bone on energy metabolism is still under thorough investigation. TGF-β superfamily is important for the development and maintenance of skeleton and is also participate in energy expenditure, while mTOR signaling is a key regulator for energy metabolism. With the help of animal models with partial ablation of osteoblasts and several other specific conditional knock out mice, we are able to examine the roles of TGF-β/mTOR signaling pathway on appetite,and thermogenesis, either in a autocrine or endocrine mode and explore its mechanism. Our project may help to clarify the common pathogenesis of bone loss, increase of body weight and narrow down the therapeutic targets. It will definitely provide solid evidence and rational to develop therapeutic agents regulating appetite, and bone mineral density.