Noninvasive Measurement of UCP1 in Brown Adipose Tissue

描述（由申请人提供）：我们正处于肥胖和糖尿病的全球流行之中。根据世界卫生组织的数据，超过10亿成年人（约占世界人口的15%）超重（体重指数（BMI） bbb25）或肥胖（BMI bbb30），超过1.5亿成年人患有糖尿病，其中大多数是由与肥胖相关的胰岛素抵抗引起的2型糖尿病。至少有两种明显可区分的脂肪：储存能量的白色脂肪组织（WAT）和燃烧能量产生热量的棕色脂肪组织（BAT）。因此，一个人有多“胖”不仅反映了他/她吃了多少，还反映了WAT和BAT的含量以及BAT的活性。评估BAT的数量和活性的方法对于评估增加BAT产热以减少肥胖的策略至关重要。我们建议设计和测试能够感知UCP1 mRNA存在的新型RNA分子，UCP1 mRNA是BAT存在和活性的标记物。这些新rna将成为核糖开关的一部分，当生物标志物存在时，激活相关的适体，该适体将结合放射性分子123I甲状腺激素，可以用SPECT/CT定位和定量。我们将使用一种新的基于细胞的SELEX方法，研究这种核糖开关在培养BAT细胞中的传递。SPECT/CT研究将使我们能够成像和量化小鼠BAT组织中响应UCP1 mRNA存在的放射性配体的摄取和保留。结合希伯来大学医学院π的经验领域的RNA绑定,我们的顾问/合作者的专长适体选择和内化的细胞表面标记,乔斯林π的蝙蝠蝙蝠生理学和组织培养的经验,和BIDMCπ的核医学的专业知识,这个项目提出了,据我们所知,一个全新的方法来明确目标和量化UCP1 mRNA,蝙蝠的存在和活动的一个关键标志。

DESCRIPTION (provided by applicant): We are in the midst of worldwide epidemics of obesity and diabetes. According to the World Health Organization, over 1 billion adults (~15% of the world population) are either overweight (body mass index (BMI) >25) or obese (BMI>30) and more than 150 million adults have diabetes, most of which is type 2 diabetes driven by the insulin resistance associated with obesity. There are at least two clearly distinguishable forms of fat: white adipose tissue (WAT), which stores energy, and brown adipose tissue (BAT), which burns energy for thermogenesis. Thus, how "fat" an individual is not just a reflection of how much s/he eats, but also how much WAT vs. BAT might be present and how active the BAT might be. Methods for evaluating the amount and activity of BAT are crucial for evaluating strategies to increase BAT thermogenesis in order to reduce obesity. We propose to design and test novel RNA molecules that will sense the presence of UCP1 mRNA, a marker for the presence and activity of BAT. These novel RNAs will be part of a riboswitch that, when the biomarker is present, activates an associated aptamer, that will bind a radioactive molecule, 123I thyroid hormone, which can be localized and quantitated with SPECT/CT. We shall investigate delivery of this riboswitch into BAT cells in culture, using a novel cell based SELEX approach. SPECT/CT studies will enable us to image and quantitate the uptake and retention of a radioactive ligand responsive to the presence of UCP1 mRNA in BAT tissue in mice. By combining the Hebrew University Medical School PI's experience in the field of RNA binding, our consultant/collaborators' expertise in aptamer selection and internalization of cell surface markers, the Joslin PI's experience in BAT physiology and BAT tissue culture, and the BIDMC PI's expertise in nuclear medicine, this project proposes, to the best of our knowledge, a completely novel approach to specifically target and quantitate UCP1 mRNA, a key marker for the presence and activity of BAT.