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

项目总结 肥胖在美国已经成为一种流行病，影响着超过三分之一的美国成年人和 增加糖尿病和其他合并症的发生率。减肥引发适应性代谢和 荷尔蒙变化，类似于饥饿时的变化，这会使减轻的体重保持得更多 很有挑战性。这些变化包括能源消耗的下降幅度大于预期 仅根据身体成分的变化就可以预测。在啮齿类动物中，很早以前就已经确定棕色 脂肪组织(BAT)是适应性产热或能量消耗调节的主要场所 在寒冷暴露和过度进食期间产生热量。新出现的数据表明，激活的蝙蝠可能会影响 人体的体重、核心体温、能量消耗以及血糖和脂肪代谢。 辣椒素是辣椒素的非刺激性类似物，它通过刺激脑组织中的感觉神经元来激活蝙蝠。 胃肠道。长期摄入类头孢菌素可能会刺激新蝙蝠的发育或招募 白色脂肪组织仓库中的前体干细胞。拟议研究的主要目标是 确定长期摄入类仙人掌是否可以在缺乏蝙蝠或仅仅 在已经拥有蝙蝠的人中激活蝙蝠。其他目标是1)确定常见的遗传变异 影响对辣椒素的反应，2)确定慢性摄入辣椒素和BAT对代谢的影响 肥胖者在没有体重减轻的情况下的激活以及3)确定慢性摄取衣壳蛋白和BAT激活 通过低卡路里饮食改善减肥效果。42名年龄在18-45岁的肥胖男性志愿者将被招募参加一项 辣椒素补充剂的随机、双盲、安慰剂对照试验。这项研究将包括两个部分 阶段：第一阶段，受试者在8周内保持他们通常的饮食和活动水平，第二阶段 受试者食用12周的低卡路里饮食。将在每个阶段之前和之后研究主题，包括 测量BAT、核心体温、安静时、冷暴露后和测试后的能量消耗 一顿试餐后的膳食、身体成分、血糖和胰岛素水平。BAT的特征将使用 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) 技巧。如果初步数据得到证实，BAT通过慢性衣壳蛋白进行招募和激活 补充可能成为一种安全的方法，以对抗能源消耗的适应性变化，这些变化 肥胖表现为体重减轻。

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.