Non-invasive assessment of human brown adipose tissue mass and activity

人体棕色脂肪组织质量和活性的无创评估

• 批准号: 9261986
• 负责人: Theodore F. Towse
• 金额: $ 5.7万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9261986
• 关键词: Non; invasive; assessment; human; brown

 DESCRIPTION (provided by applicant): Brown adipose tissue (BAT) has garnered widespread attention recently due to its potential involvement in weight maintenance, blood lipid metabolism and glucose homeostasis. Although research in animals (mainly mice and rats) supports an inverse relationship between BAT and the development of metabolic syndrome, very little is known about the function of BAT in humans (hBAT). The reason for our limited understanding may be due in part to the lack of appropriate techniques for studying hBAT. The technique most commonly used to study hBAT is 18F-FDG PET, which has come under scrutiny because it only detects BAT that takes up glucose (not the preferred energy substrate of BAT). Therefore, 18F-FDG PET likely underreports the prevalence of hBAT. Our group has recently developed robust MRI-based techniques to study hBAT non- invasively, and without the use of radioactively labeled tracers. We will use these techniques to provide an accurate assessment of the prevalence and thermogenic activity of hBAT as well as to investigate the influence of physical activity, sex, age, body composition and diabetes status on hBAT. We will study hBAT in adults using two magnetic resonance imaging (MRI) techniques available on a 3 Tesla human MRI scanner. First, fat signal fraction (FSF) maps obtained from fat-water separated MRI can localize hBAT and estimate BAT volume and mass. Maps of FSF can distinguish BAT because it contains a higher proportion of water compared to white adipose tissue (WAT), while also containing a higher lipid fraction than lean tissue. The second MRI technique is a recently developed advanced fat-water thermometry technique that measures the absolute shift in the water peak resulting from a change in temperature. Lipid signals, which are not affected by temperature, serve as a built-in reference allowing the measurement of absolute temperature in tissues containing both water and lipid signals - a hallmark of brown adipose tissue. Subjects will also undergo indirect calorimetry. Mass and the thermogenic activity of hBAT will be assessed in each subject using two distinct experimental protocols using either cold-stimulation or a meal-challenge. In this study, we will pursue the following three Specific Aims: [1] Investigate the impact of physical activity and sex on BAT mass and activity in adult humans. [2] Investigate the impact of age and body composition on BAT mass and activity in adult humans. [3] Investigate the impact of diabetes on BAT mass and activity in adult humans. Impact: Reliable characterization of hBAT mass and activity in healthy and clinically relevant subjects is critical for the pursuit of longitudinal interventional studies by clinical investigatos to therapeutically enhance hBAT to counteract metabolic diseases.

 描述（申请人提供）：棕色脂肪组织（BAT）由于其在体重维持、血脂代谢和葡萄糖稳态中的潜在参与作用，最近引起了广泛的关注。尽管对动物（主要是小鼠和大鼠）的研究支持 BAT 与代谢综合征的发展之间存在负相关关系，但人们对 BAT (hBAT) 的功能知之甚少。我们理解有限的部分原因可能是缺乏研究 hBAT 的适当技术。最常用于研究 hBAT 的技术是 18F-FDG PET，该技术已受到严格审查，因为它仅检测吸收葡萄糖的 BAT（不是 BAT 的首选能量底物）。因此，18F-FDG PET 可能低估了 hBAT 的患病率。我们的小组最近开发了强大的基于 MRI 的技术来非侵入性地研究 hBAT，并且不使用放射性标记的示踪剂。我们将利用这些技术准确评估 hBAT 的患病率和生热活性，并研究体力活动、性别、年龄、身体成分和糖尿病状况对 hBAT 的影响。我们将使用 3 特斯拉人体 MRI 扫描仪上提供的两种磁共振成像 (MRI) 技术来研究成人的 hBAT。首先，从脂水分离 MRI 获得的脂肪信号分数 (FSF) 图可以定位 hBAT 并估计 BAT 体积和质量。 FSF 图可以区分 BAT，因为与白色脂肪组织 (WAT) 相比，它含有更高比例的水，同时也比瘦肉组织含有更高比例的脂质。第二种 MRI 技术是最近开发的先进的脂肪-水测温技术，可测量温度变化引起的水峰的绝对偏移。脂质信号不受温度影响，可作为内置参考，允许测量同时含有水和脂质信号（棕色脂肪组织的标志）的组织中的绝对温度。受试者还将接受间接量热法。将使用冷刺激或膳食挑战两种不同的实验方案来评估每个受试者的 hBAT 质量和生热活性。在这项研究中，我们将追求以下三个具体目标： [1] 调查体力活动和性别对成年人 BAT 质量和活动的影响。 [2] 研究年龄和身体成分对成年人 BAT 质量和活动的影响。 [3] 研究糖尿病对成年人 BAT 质量和活性的影响。影响：健康和临床相关受试者中 hBAT 质量和活性的可靠表征对于通过临床研究进行纵向介入研究以治疗增强 hBAT 以对抗代谢疾病至关重要。