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

基本信息

批准号：
9241559
负责人：
Jie Deng
金额：
$ 44.99万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
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/9241559
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 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 Heating 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 TRPV1 gene Testing Thermogenesis Tissues United States Vanilloid Variant X-Ray Computed Tomography abdominal fat analog base 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

项目摘要

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.

项目概要肥胖已成为美国的一种流行病，影响了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病率。减肥引发适应性代谢和荷尔蒙的变化，类似于饥饿时所见的变化，这使得维持减轻的体重更加容易具有挑战性的。这些变化包括能量消耗的减少，其幅度大于仅根据身体成分的变化进行预期。在啮齿类动物中，人们早已确定棕色脂肪组织（BAT）是适应性产热或能量消耗和调节的主要场所寒冷暴露和过度喂养时会产生热量。新数据表明，激活 BAT 可能会影响人体体重、核心体温、能量消耗以及血糖和脂肪代谢。 Capsinoids 是辣椒素的无刺激性类似物，通过刺激大脑中的感觉神经元来激活 BAT 胃肠道。长期摄入辣椒素可能会刺激新 BAT 的发育或招募来自白色脂肪组织库内的前体干细胞。拟议研究的主要目标是确定长期摄入辣椒素是否可以在缺乏 BAT 或仅仅补充 BAT 的肥胖个体中招募 BAT 激活已经拥有 BAT 的人。其他目标是 1) 确定是否存在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 的代谢影响 3) 确定慢性辣椒素摄入和 BAT 激活是否有关通过低热量饮食改善减肥效果。将招募 42 名年龄在 18 岁至 45 岁之间的肥胖男性志愿者进行一项补充辣椒素的随机、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平常的饮食和活动水平 8 周，第二个阶段是受试者持续 12 周采用低热量饮食。每个阶段之前和之后都会对科目进行研究，包括测量 BAT、核心体温、休息时、寒冷暴露后和测试后的能量消耗膳食、身体成分以及测试餐后的血糖和胰岛素水平。 BAT 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。如果初步数据得到证实，BAT 通过慢性辣椒素募集和激活补充可能会成为一种安全的方法来应对能量消耗的适应性变化可见于肥胖者的体重减轻。