中文摘要
激活的棕色脂肪(BAT)能加速对脂质和葡萄糖的代谢,而目前国际广泛使用的[18F]FDG PET成像仅基于局部糖代谢来间接评估BAT功能,无法直接评估BAT线粒体活性改变。TSPO为特异性表达于线粒体膜上的转运蛋白,BAT富含线粒体且高表达TSPO。我们的预实验结果观察到TSPO靶向示踪剂[18F]DPA-714在小鼠BAT部位浓聚。因此,我们提出假说,TSPO靶向PET成像可活体显示不同状态下BAT中线粒体活性变化。为验证这一假说,我们拟首先验证[18F]DPA-714与BAT表达的TSPO的结合特异性,然后观察激活状态下BAT摄取[18F]DPA-714的变化,最后评估正常鼠和肥胖鼠BAT摄取[18F]DPA-714能力的差异。以上实验将能够证明TSPO PET成像可以作为一种新的BAT活体研究手段,为深入研究不同状态下BAT的线粒体活性变化及其与BAT代谢改变间的关系奠定基础。
英文摘要
Brown adipose tissue (BAT) is an important heat-producing tissue in mammals. It can consume a large amount of fatty acid and glucose for non-shivering heat production. Hence, it plays a key role in body energy balance and undoubtedly becomes a potential target for anti-obesity treatment. Currently, [18F]FDG PET imaging is the most common method used for in vivo BAT study. However, it only relies on local glucose metabolism and cannot be used for directly evaluating mitochondria activity in activated BAT. Translocator protein (18KDa) (TSPO) localizes on the mitochondrial membrane of different organs including BAT and it involves in fatty digestion. Interestingly, in our previous study using TSPO-targeted PET tracer [18F]DPA-714 for neuroinflammation imaging, we found that there was a high tracer uptake in mouse interscapular BAT area. On account of the above mentioned findings, here we hypothesize that TSPO-targeted PET imaging can be used for in vivo evaluating mitochondria activation in BAT under different conditions. In order to prove this, we will at first investigate the specificity of [18F]DPA-714 binding with TSPO expressed in BAT both in vivo and ex vivo. Then, the change of [18F]DPA-714 uptake in activated BAT will be evaluated . Finally, we will compare the tracer uptake in BAT of both wild mice and obesity mice after BAT activation. In summary, this study will provide a brand new method for in vivo BAT imaging. It may help to understand the relationship between BAT activation and mitochondria activity.
