米色脂肪分化在肥胖发生及其调控因素中的分子影像机制研究

Obesity with continuously high prevalence rate and hard to be cured has become one of the most important non-infective epidemic diseases threatening modern social public health. We try to find a solution from browning of white adipose tissue using obesity rat model evaluated by a molecular imaging modality called microPET. The brown adipocytes appearing in WAT are often called beige adipocytes. Understanding the biological processes controlling beige adipocyte activity and differentiation could help the design of effective strategies to increase energy expenditure and fight against obesity. 18F-FDG uptake changes reveal the function state of beige adipocyte in vivo accurately and quantitively. Statistical parametric mapping (SPM) software can help us to evaluate the brain glucose metabolism changes after applying various regulatory factors, such as medicine and diet..The ultimate goals of our molecular imaging research are to identify key regulatory factors elucidate the molecular mechanisms involved in the differentiation of beige adipocytes, evaluate the novel preventive and therapeutic interventions that are aimed at alleviating the substantial suffering and dysfunction obesity imposes.

肥胖症目前已经成为威胁现代社会公共健康最主要的非传染性流行病之一。针对其持续高发和难治性，本课题将利用肥胖鼠模型，通过小动物正电子发射断层显像（microPET）研究，从激活白色脂肪细胞棕色化为米色脂肪细胞的角度探索解决途径。动态观察各种调控因素（药物、温度、饮食等）肥胖鼠脂肪组织对于18F-FDG摄取的变化，分析影响脂肪组织功能的因素及与肥胖鼠生化指标的内在联系，建立活体、准确、定量评估米色脂肪功能状态的可靠方法；同时用统计参数图（SPM）定量比较分析肥胖鼠调控前后大脑各功能区葡萄糖能量代谢状态的差异。本课题将利用microPET 分子影像方法揭示米色脂肪分化与肥胖症病程的内在联系，评价各种调控因素对体内及脑内葡萄糖代谢状态的改变情况，为探索肥胖症治疗及疗效评估提供新的思路。

课题针对肥胖症持续高发和难治性，利用肥胖鼠模型，通过小动物正电子发射断层显像(microPET)研究， 动态观察各种调控因素(药理、生理等)肥胖鼠脂肪组织对于18F-FDG摄取的变化，同时用统计参数图(SPM)定量比较分析肥胖鼠调控前后大脑各功能区葡萄糖能量代谢状态的差异。microPET 分子影像方法揭示米色脂肪分化与肥胖症病程的内在联系，评价各种调控因素对体内及脑内葡萄糖代谢状态的改变情况，为探索肥胖症治疗及疗效评估提供新的思路。运动训练组大鼠右侧第二视觉皮层、左侧纹状体、左侧耳蜗核[18F]FDG摄取增高，而扣带回摄取减低。单用药物消退组右侧第一视觉皮层、左侧海马区[18F]FDG摄取增高，而双侧第一躯体感觉皮层、双侧第一运动皮层及楔束核摄取减低。行为训练联合药物消退组左侧海马区、左侧纹状体、左侧深部脑白质、右侧胼胝体及右侧岛叶[18F]FDG摄取增高，而双侧锥体系、右侧旁正中小叶摄取减低。我们发现肥胖组大鼠在消退过程中产生类似应激障碍焦虑情绪等的相似脑区改变，前额叶-杏仁核 -海马环路中杏仁核活动增强是产生精神创伤相关记忆的关键神经区域。