白色脂肪棕色化的神经内分泌调控新通路：α7nAChR-ORM机制

白色脂肪棕色化是代谢及心脑血管疾病治疗新方向，但机制远未阐明。胆碱能抗炎通路是机体重要迷走神经通路，α7nAChR是其关键受体。前期发现：α7nAChR敲除小鼠白色脂肪棕色化功能受损，能耗下降，提示该神经通路调节白色脂肪棕色化。课题组自行构建的脂肪因子ORM敲除小鼠出现同样表型，且外源性ORM直接促进小鼠和细胞白色脂肪向棕色化转变。进一步发现，α7nAChR激活特异促进脂肪、肝脏ORM表达，提示ORM介导胆碱能抗炎通路α7nAChR对白色脂肪棕色化的调节。课题将首先证明胆碱能抗炎通路通过α7nAChR调节白色脂肪棕色化和能量消耗，其次明确ORM介导胆碱能抗炎通路的这一作用，最后阐明ORM调控白色脂肪棕色化的分子机制，以期系统阐明白色脂肪棕色化的神经内分泌调控新通路：α7nAChR-ORM机制。这是机体调控能量代谢理论体系的重要补充，α7nAChR或ORM可能成为白色脂肪棕色化药物研发新靶点

Browning of white adipose is a new direction for the cardiovascular and metabolic diseases, but the mechanisms remain largely unknown. Cholinergic anti-inflammatory pathway is one of important vagus pathways, and α7nAChR is the key receptor. We previous found that α7nAChR- deficient mice showed a significant decrease in energy expenditure and browning genes, indicating its role in the browning of white adipose. ORM- deficient mice constructed by our lab also showed similar phenotypes, and exogenous ORM can directly promoted browning of white adipose. Furthermore, specific agonist for α7nAChR could induce ORM expression in white adipose and liver tissue. These data suggest that ORM might be involved in the regulation of cholinergic anti-inflammatory pathway in the browning of white adipose. Here, we will first demonstrate that cholinergic anti-inflammatory pathway regulates the browning of white adipose and energy expenditure via α7nAChR, then clarify that ORM mediates this role, lastly explore the signal pathway of ORM in the browning of white adipose. We first creatively raised a novel identified nerve-endocrine pathway that regulates the browning of white adipose and energy metabolism via α7nAChR and its downstream ORM, which is an important new theory in the control of energy metabolism. ORM or α7nAChR might act as new targets for the browning of white adipose.