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

辣椒素类化合物对肥胖中棕色脂肪组织募集和激活的影响

• 批准号: 9355632
• 负责人: Jie Deng
• 金额: $ 43.55万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9355632
• 关键词: Acclimatization; Adipose tissue; Adult; Affect; Afferent Neurons; Age; American; Blood Glucose; Blood flow; Body Composition; Body Temperature; Body Weight; Body Weight decreased; Brown Fat; Calories; Capsaicin; Capsicum; Cell Respiration; Chronic; Comorbidity; Data; Development; Diabetes Mellitus; Diet; Diffusion; Dose; Energy Metabolism; Epidemic; Fatty Acids; Fatty acid glycerol esters; Gastrointestinal tract structure; Generations; Genes; Genetic Polymorphism; Goals; Hormonal Change; Human; Image; Imaging Techniques; Incidence; Individual; Ingestion; Insulin; Intervention; Magnetic Resonance Imaging; Maintenance; Measurement; Measures; Mediating; Metabolic; Methods; Obesity; Phase; Placebos; Play; Positron-Emission Tomography; Property; Randomized; Recruitment Activity; Research; Rest; Rodent; Role; Site; Starvation; Stem cells; Structure; Supplementation; Testing; Thermogenesis; Thinness; Tissues; United States; Vanilloid; Variant; Weight Gain; X-Ray Computed Tomography; abdominal fat; analog; combat; design; dietary supplements; double-blind placebo controlled trial; genetic variant; glucose metabolism; improved; indexing; insulin sensitivity; lipid metabolism; male; men; novel; oxidation; prevent; randomized placebo controlled trial; receptor; response; treatment effect; volunteer

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.

项目摘要 肥胖已成为美国的流行病，影响了美国成年人的三分之一以上 增加糖尿病和其他合并症的发生率。减肥引起自适应代谢和 荷尔蒙变化，类似于饥饿中看到的荷尔蒙变化，从而使体重减轻减轻 具有挑战性的。这些变化包括能源消耗的减少，大于 仅基于人体成分的变化而预期。在啮齿动物中，长期以来已经确定了棕色 脂肪组织（BAT）是自适应热发生或能量消耗和调节的主要部位 在冷暴露和过度喂养过程中产生热量。新兴数据表明，激活的蝙蝠可能会影响 人体体重，核心体温，能量消耗以及人类的血糖和脂肪代谢。 辣椒素是辣椒素的nunpungent类似物，通过刺激感觉神经元激活蝙蝠 胃肠道。长期摄入辣椒素可能会刺激新蝙蝠的发展或募集 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 确定长期摄入辣椒素是否可以招募缺乏帽或仅仅是肥胖的个体 在已经拥有它的人中激活蝙蝠。其他目标是1）确定是否常见遗传变异 影响对辣椒素的反应，2）确定慢性衣壳摄入和BAT的代谢作用 肥胖症激活而无需减肥，3）确定慢性衣壳摄入和蝙蝠是否激活 通过低卡路里饮食改善体重减轻。 42名肥胖男性志愿者，年龄在18-45岁，将被招募 随机，双盲，安慰剂对照的补充试验。该研究将由两个 阶段：第一个受试者在8周内维持其通常的饮食和活动水平，第二个。 受试者食用低热量饮食12周。每个阶段之前和之后将研究受试者，包括 蝙蝠的测量，核心体温，静止时的能量消耗，冷暴露后以及测试后 测试餐后的餐，身体成分以及血糖和胰岛素水平。蝙蝠将使用 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） 技术。如果确认了初步数据，请通过慢性辣椒素募集和激活 补充可以作为一种安全的方法来打击能量消耗的自适应变化 看到肥胖症的体重减轻。