Noninvasive Measurement of UCP1 in Brown Adipose Tissue

棕色脂肪组织中 UCP1 的无创测量

• 批准号: 8302245
• 负责人: C RONALD KAHN
• 金额: $ 25.5万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8302245
• 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）：我们正处于肥胖和糖尿病的全球流行病中。根据世界卫生组织的数据，超过10亿成年人（占世界人口的约15％）是超重（体重指数（BMI）> 25）或肥胖（BMI> 30），超过1.5亿成年人患有糖尿病，其中大部分是由胰岛素抵抗造成的2型糖尿病。至少有两种明显区分的脂肪形式：白色脂肪组织（WAT），该脂肪组织（WAT）存储能量和棕色的脂肪组织（BAT），它们燃烧能量以进行热生成。因此，一个人的“胖”不仅反映出他/他吃了多少，而且还反映了可能存在多少水与蝙蝠，蝙蝠的活跃程度。评估BAT的数量和活动的方法对于评估增加BAT生热的策略以减少肥胖至关重要。我们建议设计和测试新型的RNA分子，以感觉到UCP1 mRNA的存在，UCP1 mRNA是蝙蝠的存在和活性的标志。这些新型的RNA将是核糖开关的一部分，当存在生物标志物时，它会激活相关的适体，该适体将结合放射性分子，即123i甲状腺激素，可以将其定位并用SPECT/CT进行定量。我们将使用新型的基于细胞的SELEX方法来研究这种核糖开关在培养物中的蝙蝠细胞中的递送。 SPECT/CT研究将使我们能够形象和定量对小鼠蝙蝠组织中UCP1 mRNA的响应的放射性配体的摄取和保留。通过结合希伯来大学医学院PI在RNA绑定领域的经验，我们的顾问/合作者在适体选择和内部化细胞表面标记方面的专业知识，Joslin Pi在蝙蝠生理学和蝙蝠组织培养中的经验以及BIDMC PI在核医学方面的专业知识，该项目的最佳方法是，该项目的主要范围，并提出了一定的目标。蝙蝠的存在和活动。