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

 描述（由申请人提供）：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，最近引起了广泛的关注。虽然在动物（主要是小鼠和大鼠）中的研究支持BAT与代谢综合征的发展之间的反向关系，但对BAT在人类中的功能（hBAT）知之甚少。我们的理解有限的原因可能部分是由于缺乏适当的技术来研究hBAT。最常用于研究hBAT的技术是18F-FDG PET，该技术受到了严格的审查，因为它只能检测摄取葡萄糖的BAT（而不是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。我们将使用这些技术来提供一个准确的评估的患病率和产热活动的hBAT，以及调查的影响，体力活动，性别，年龄，身体成分和糖尿病的hBAT状态。我们将使用两种磁共振成像（MRI）技术在3特斯拉人体MRI扫描仪上研究hBAT。首先，从脂肪-水分离的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图谱可以区分BAT，因为与白色脂肪组织（WAT）相比，它含有更高比例的水，同时还含有比瘦肉组织更高的脂质部分。第二种MRI技术是最近开发的先进的脂肪-水温度测量技术，其测量由温度变化引起的水峰的绝对偏移。不受温度影响的脂质信号可作为内置参考，用于测量含有水和脂质信号的组织中的绝对温度-这是棕色脂肪组织的标志。受试者还将接受间接热量测定。将使用两种不同的实验方案，使用冷刺激或膳食激发，在每个受试者中评估hBAT的质量和产热活性。在这项研究中，我们将追求以下三个具体目标：[1]调查身体活动和性别对成年人BAT质量和活动的影响。[2]调查年龄和身体成分对成年人BAT质量和活性的影响。[3]研究糖尿病对成年人BAT质量和活性的影响。影响：在健康和临床相关受试者中hBAT质量和活性的可靠表征对于临床医生进行纵向干预研究以治疗性地增强hBAT对抗代谢疾病至关重要。

 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.