Noninvasive Measurement of UCP1 in Brown Adipose Tissue

棕色脂肪组织中 UCP1 的无创测量

• 批准号: 8189215
• 负责人: C RONALD KAHN
• 金额: $ 20万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8189215
• 关键词: Adipose tissue; Adult; Affinity; Animals; Binding; Binding Sites; Biological Assay; Biological Markers; Blood; Blood Circulation; Body Weight decreased; Body mass index; Brown Fat; Burn injury; CD3 Antigens; Calories; Cell Line; Cell surface; Cells; Chimera organism; Critiques; Diabetes Mellitus; Discipline of Nuclear Medicine; Eating; Ensure; Epidemic; Face; Fatty acid glycerol esters; Half-Life; Hormones; Image; Incubated; Individual; Injection of therapeutic agent; Insulin Resistance; Label; Ligands; Measurement; Messenger RNA; Methods; Modification; Mus; NF-kappa B; Non-Insulin-Dependent Diabetes Mellitus; Nucleotides; Obesity; Outcome; Overweight; Physiology; Population; Positioning Attribute; Process; Published Comment; RNA; RNA Binding; RNA Degradation; RNA Stability; RNA library; Radioactive; Radioactivity; Rest; Screening procedure; Serum; Small RNA; System; Techniques; Testing; Thermogenesis; Thyroid Hormones; Time; Tissues; Toxic effect; Triiodothyronine; Universities; World Health Organization; aptamer; base; clinical trials in animals; design; experience; in vivo; medical schools; meetings; novel; novel strategies; research study; single photon emission computed tomography; tissue culture; uptake

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.

描述（由申请人提供）：我们正处于全球肥胖和糖尿病流行之中。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) >25）或肥胖（BMI>30），超过 1.5 亿成年人患有糖尿病，其中大多数其中2型糖尿病是由与肥胖相关的胰岛素抵抗引起的。脂肪至少有两种明显可区分的形式：储存能量的白色脂肪组织（WAT）和燃烧能量以产热的棕色脂肪组织（BAT）。因此，一个人的“肥胖”程度不仅反映了他/她吃了多少，还反映了 WAT 与 BAT 的含量以及 BAT 的活跃程度。评估 BAT 数量和活性的方法对于评估增加 BAT 生热作用以减少肥胖的策略至关重要。我们建议设计和测试新型 RNA 分子，该分子将感知 UCP1 mRNA 的存在，UCP1 mRNA 是 BAT 存在和活性的标记。这些新型RNA将成为核糖开关的一部分，当生物标志物存在时，核糖开关会激活相关的适体，该适体将结合放射性分子123I甲状腺激素，可以通过SPECT/CT对其进行定位和定量。我们将使用一种新的基于细胞的 SELEX 方法研究将这种核糖开关传递到培养的 BAT 细胞中。 SPECT/CT 研究将使我们能够对小鼠 BAT 组织中 UCP1 mRNA 存在的放射性配体的摄取和保留进行成像和定量。通过结合希伯来大学医学院 PI 在 RNA 结合领域的经验、我们的顾问/合作者在适体选择和细胞表面标记内化方面的专业知识、Joslin PI 在 BAT 生理学和 BAT 组织培养方面的经验以及 BIDMC PI 在在核医学领域，据我们所知，该项目提出了一种全新的方法来特异性靶向和定量 UCP1 mRNA，UCP1 mRNA 是核医学存在和活性的关键标志物。最佳可行技术。