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

 描述(申请人提供)：棕色脂肪组织(BAT)最近引起了广泛的关注，因为它可能参与体重维持、血脂代谢和血糖稳态。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相反的关系，但对BAT在人类中的功能(HBAT)知之甚少。我们认识有限的部分原因可能是缺乏适当的技术来研究hBAT。最常用的研究hBAT的技术是18F-FDG PET，因为它只检测吸收葡萄糖的BAT(不是BAT的首选能量底物)，所以受到了密切关注。因此，18F-FDG PET可能低估了hBAT的患病率。我们小组最近开发了基于MRI的强大技术来非侵入性地研究hBAT，并且不使用放射性标记示踪剂。我们将使用这些技术来准确评估hBAT的患病率和生热活性，并调查体力活动、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特斯拉人体核磁共振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，从脂肪和水分离的MRI获得的脂肪信号分数(FSF)图可以定位hBAT并估计BAT的体积和质量。FSF的MAP图可以区分蝙蝠，因为与白色脂肪组织(WAT)相比，BAT含有更高比例的水分，同时也含有比瘦组织更高的脂肪成分。第二种核磁共振技术是最近开发的一种先进的脂肪-水测温技术，它测量温度变化导致的水峰的绝对位移。脂肪信号不受温度的影响，作为内置基准，允许测量包含水和脂肪信号的组织的绝对温度-这是棕色脂肪组织的标志。受试者还将接受间接量热法。HBAT的质量和生热活性将在每个受试者中使用两种不同的实验方案进行评估，使用冷刺激或进餐挑战。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类蝙蝠质量和活动的影响。[2]研究年龄和身体成分对成年人类蝙蝠质量和活动量的影响。[3]研究糖尿病对成年人类蝙蝠质量和活动的影响。影响：可靠地表征健康和临床相关受试者的hBAT质量和活性，对于临床研究从治疗上增强hBAT以对抗代谢性疾病进行纵向干预性研究至关重要。

 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.