The impact of estrogen status on the biological function of brown adipose tissue in women measured using quantitative PET/CT

使用定量 PET/CT 测量雌激素状态对女性棕色脂肪组织生物学功能的影响

• 批准号: 9353399
• 负责人: Edward L Melanson
• 金额: $ 58.96万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-16 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9353399
• 关键词: Acetates; Acute; Adipose tissue; Affect; Agonist; Attenuated; Back; Behavioral; Biological Process; Body Composition; Body Weight; Brown Fat; Cell Respiration; Chronic Disease; Data; Deoxyglucose; Development; Energy Metabolism; Estradiol; Estrogens; Fatty acid glycerol esters; Female; Gender Role; Goals; Gonadal Steroid Hormones; Gonadotropin Hormone Releasing Hormone; Human; Image; Impairment; Intervention; Lead; Luteal Phase; Measures; Mediating; Menopause; Menstrual cycle; Metabolic; Metabolic Clearance Rate; Obesity; Obesity associated disease; Ovarian; Ovarian Ablation; Ovarian hormone; Pharmacology; Phase; Physiological; Population; Positron; Positron-Emission Tomography; Postmenopause; Premenopause; Research; Rest; Risk; Rodent; Role; Series; Serum; Shivering; Skin; Steroids; Stimulus; Strategic Planning; Support System; Sympathetic Nervous System; Temperature; Thermogenesis; Tracer; Treatment Efficacy; United States National Institutes of Health; Visceral; Weight Gain; Woman; Women' s Role; X-Ray Computed Tomography; energy balance; in vivo; men; obesity risk; preclinical study; prevent; response; time interval; uptake

Project Summary The physiological relevance of brown adipose tissue in humans is largely unknown. We have shown that suppressing ovarian function in premenopausal women reduces resting energy expenditure (REE), and this is prevented by adding back estradiol (E2). Our preliminary data suggest that this may be due, in part, to reduced brown adipose tissue (BAT) activity. There is also compelling evidence from basic and pre-clinical studies that BAT function and thermogenic activity is modulated by E2. However, whether E2 status affects BAT activity in women has not been studied. Our overarching hypothesis is that BAT activity in humans is modulated by E2. In this research, we will study 1) the contribution of BAT to REE under basal (room temperature) and stimulated conditions (mild cold-exposure); and 2) whether these responses are modulated by E2 status. To determine if natural declines in endogenous E2 contribute to changes in BAT activity, we will compare BAT activity in pre- and post-menopausal women. We will also explore whether suppression of ovarian hormones in pre- menopausal women impairs BAT activity. BAT activity will be quantified using dynamic positron emission topography/computed tomography (PET/CT) imaging combined with 11C-acetate tracers. We will assess the thermogenic response of BAT by measuring cold-induced changes in REE, shivering, and skin and core temperature. The proposed research is well-aligned with two of the primary objectives of RFA-DK-15-031, which are 1) to explore the biological functions of BAT in humans; and 2) determine conditions that modulate its activity in humans. Studying E2-mediated effects on BAT and REE will increase our understanding of how the loss of ovarian function during the menopausal transition contributes to weight gain and an increase in visceral adipose tissue, increasing the risk of obesity-related chronic diseases. This could lead to development of behavioral or pharmacologic interventions to attenuate decreases in REE and reduce risk for weight gain.

项目摘要 人类棕色脂肪组织的生理相关性在很大程度上是未知的。我们已经证明了 抑制绝经前妇女的卵巢功能会减少静息能量消耗(REE)，这是 通过补充补充雌二醇(E2)来预防。我们的初步数据表明，这可能在一定程度上是由于 棕色脂肪组织(BAT)活性。基础和临床前研究也有令人信服的证据表明 BAT的功能和生热活性受E2的调节。然而，E2状态是否会影响BAT的活性 女性还没有被研究过。我们最重要的假设是，人类体内的BAT活动受到雌二醇酮的调节。在……里面 在本研究中，我们将研究1)基础(室温)和刺激条件下BAT对稀土元素的贡献 条件(温和的冷暴露)；2)这些反应是否受E2状态的调节。要确定是否 内源性E2的自然下降有助于BAT活性的变化，我们将比较BAT在 以及绝经后的女性。我们还将探索卵巢激素的抑制是否在前 更年期妇女会损害蝙蝠的活动。BAT活动将使用动态正电子发射进行量化 地形图/计算机断层扫描(PET/CT)结合11C-醋酸酯示踪剂。我们将评估 通过测量冷诱导的REE、颤抖、皮肤和核心的变化来测量蝙蝠的生热反应 温度。拟议的研究与RFA-DK-15-031的两个主要目标非常一致， 它们是：1)探索蝙蝠在人体内的生物学功能；2)确定调节蝙蝠活动的条件 它在人类体内的活动。研究E2对BAT和REE的影响将增加我们对 绝经过渡期间卵巢功能的丧失会导致体重增加和体重增加 内脏脂肪组织，增加肥胖相关慢性病的风险。这可能会导致发展 通过行为或药物干预来减缓稀土元素的减少，降低体重增加的风险。