The effects of capsinoids on brown adipose tissue recruitment and activation in obesity

项目摘要 肥胖在美国已经成为一种流行病，影响了超过三分之一的美国成年人， 增加糖尿病和其他合并症的发病率。减肥有助于适应性代谢和 荷尔蒙的变化，类似于饥饿时所见的变化，这使得维持减少的体重变得更加重要。 挑战性这些变化包括能量消耗的减少， 仅根据身体成分的变化就可以预测。在啮齿类动物中，长期以来一直认为棕色 脂肪组织（BAT）是适应性产热或调节能量消耗的主要部位， 在冷暴露和过度喂养期间产生热量。新兴数据表明，激活的BAT可能会影响 体重、核心体温、能量消耗以及血糖和脂肪代谢。 辣椒酯类化合物是辣椒素的非刺激性类似物，其通过刺激大脑皮层中的感觉神经元来激活BAT。 胃肠道长期摄入辣椒酯类物质可能会刺激新BAT的发展或招募 从白色脂肪组织库中的前体干细胞。拟议研究的主要目标是 确定慢性摄入辣椒酯类物质是否可以在缺乏BAT或仅仅是BAT的肥胖个体中招募BAT 激活那些已经有BAT的人。其他目标是1）确定常见的遗传变异是否 影响对辣椒酯类物质的反应，2）确定慢性辣椒酯类物质摄入和BAT的代谢效应 3）确定慢性辣椒碱类物质摄入和BAT激活是否 用低热量饮食改善减肥效果。将招募42名年龄在18-45岁之间的肥胖男性志愿者， 辣椒碱补充剂的随机双盲安慰剂对照试验。该研究将包括两个 阶段：第一个阶段是受试者保持正常饮食和活动水平8周，第二个阶段是受试者保持正常饮食和活动水平8周 受试者食用低热量饮食12周。受试者将在每个阶段之前和之后接受研究，包括 测量BAT、核心体温、静息时、冷暴露后和测试后的能量消耗 测试餐后的膳食、身体成分、血糖和胰岛素水平。最佳可得技术的特点是， 正电子发射断层扫描/计算机断层扫描（PET/CT）和磁共振成像（MRI） 技术.如果初步数据得到证实，通过慢性辣椒碱类物质的BAT募集和激活 补充剂可能成为一种安全的方法，以对抗能量消耗的适应性变化， 在肥胖症中体重减轻。

PROJECT SUMMARY Obesity has become an epidemic in the United States, affecting more than one-third of American adults and increasing the incidence of diabetes and other comorbidities. Weight loss elicits adaptive metabolic and hormonal changes, similar to those seen in starvation, which make maintenance of a reduced body weight more challenging. These changes include a decrease in energy expenditure that is larger than what would be expected on the basis of changes in body composition alone. In rodents, it has long been established that brown adipose tissue (BAT) is the primary site of adaptive thermogenesis or the modulation of energy expenditure and heat generation during cold exposure and overfeeding. Emerging data suggest that activated BAT may influence body weight, core body temperature, energy expenditure and blood sugar and fat metabolism in humans. Capsinoids are nunpungent analogs of capsaicin that activate BAT by stimulating sensory neurons in the gastrointestinal tract. Chronic ingestion of capsinoids may stimulate the development or recruitment of new BAT from precursor stem cells within white adipose tissue depots. The primary goal of the proposed study is to determine whether chronic ingestion of capsinoids can recruit BAT in obese individuals who lack it or merely activates BAT in those who already have it. Additional goals are to 1) ascertain whether common genetic variants influence the response to capsinoids, 2) determine the metabolic effects of chronic capsinoid ingestion and BAT activation in obesity without weight loss and 3) establish whether chronic capsinoid ingestion and BAT activation improve weight loss with a low calorie diet. 42 obese male volunteers, ages 18-45, will be recruited for a randomized, double-blind, placebo-controlled trial of capsinoid supplementation. The study will consist of two phases: the first in which subjects maintain their usual diet and activity level for 8 weeks, and the second in which subjects consume a low-calorie diet for 12 weeks. Subjects will be studied before and after each phase, including measurement of BAT, core body temperature, energy expenditure at rest, after cold exposure, and after a test meal, body composition, and blood sugar and insulin levels after a test meal. BAT will be characterized using Positron Emission Tomography/Computed Tomography (PET/CT) and Magnetic Resonance Imaging (MRI) techniques. If preliminary data are confirmed, BAT recruitment and activation through chronic capsinoid supplementation may emerge as a safe method to combat the adaptive changes in energy expenditure that are seen with weight loss in obesity.