Human Energy and Body Weight Regulation Core

2015财年提交的新协议： 14-DK-0154：新陈代谢和神经对减肥、高原和恢复的适应。派·凯文·霍尔博士。ClinicalTrials.gov标识：NCT02199483。 2.15-HG-0120：西罗莫司治疗由体细胞PI3K激活引起的节段性过度生长的非随机开放标签初步研究。圆周率。医学博士金·开普勒-诺瑞尔。ClinicalTrials.gov标识：NCT02428296 3.15-DK-0174：非酒精性脂肪性肝病患者的动态餐后代谢。圆周率。亚伦·罗特曼，医学博士ClinicalTrials.gov标识：NCT02520609 研究要点： 1.我们发表了13-DK-0136的结果，这是一项与Monica Skarulis博士合作的单点随机交叉试验，研究了实验性黑素皮质素-4受体激动剂对肥胖志愿者的代谢影响。利用呼吸室的高灵敏度，我们发现，在12名健康肥胖成人研究志愿者中，实验药物RM-493(1 mg/24小时)显著增加了静息能量消耗(6.4%)和24小时脂肪氧化。这有助于我们进一步了解黑素皮质素-4在人体能量代谢中的作用。 2.我们与凯文·霍尔博士的团队一起发表了两篇论文。一项研究比较了肥胖受试者在通过减肥手术或限制卡路里和剧烈运动实现大规模减肥后，静息能量消耗和身体成分的变化，发现与正式组相比，后者导致了无脂肪质量的保存，但导致了更好的新陈代谢适应。我们进一步表明，代谢适应与能量失衡的程度和循环瘦素的变化有关。在最近的一篇论文中，我们使用从临床方案09-DK-0081收集的数据来表明，6天的选择碳水化合物与脂肪限制(等卡路里匹配每天800千卡)产生的脂肪氧化(通过室内研究测量)与碳水化合物限制不同；尽管脂肪氧化没有变化，但脂肪限制组也发现了更高的脂肪损失。这一纳入对目前低碳水化合物节食的观点提出了挑战。 3.我们最近与来自NICHD的Jack Yanovski博士团队(NCT01888939)发表了另一篇论文，这是一项随机交叉试验，研究了28名正常体重儿童(7-11岁)的久坐行为和代谢。在两个不同的日子里，孩子们要么连续坐三个小时，要么每隔半小时休息3分钟在跑步机上行走。研究参与者在实验前后通过标准的口服葡萄糖耐量测试来测试他们的血糖和胰岛素水平。当孩子们休息走路时，他们的血糖和胰岛素水平比他们连续坐着时要低。研究结果表明，当坐着被打断时，孩子们的身体能够更好地维持血糖水平。 4.我们使用了2008-2010年与冰岛心脏协会和NIA合作的独特数据集，并在2015财年发表了两篇论文。在一群居住在社区的健康的冰岛老年志愿者(平均年龄80岁)中，我们发现，尽管白天的长度和活动都对睡眠时间的模式有显著影响，但在白天长度较长和较短的时间段之间，重复者的实际个体内部差异相当微小。我们的结论是，睡眠模式和质量对日光显著变化的反应有限，可能是由于这些老年受试者的长期适应。 5.核心继续支持来自NIH 5个不同IC的19个临床方案和方案。 提供的服务(2015财年活动)：全房间呼吸室的能量消耗(311项)、代谢车的静息能量消耗(169项)、分级运动测试(109项)、实验食物行为测试(145项)和身体成分(209项DXA，98项Bod Pod)。

New protocols that were submitted in FY15: 1. 14-DK-0154: Metabolic and Neural Adaptations to Weight Loss, Plateau, and Regain. PI Kevin Hall, PhD. ClinicalTrials.gov Identifier: NCT02199483. 2. 15-HG-0120: Nonrandomized Open Label Pilot Study of Sirolimus Therapy for Segmental Overgrowth Caused by Somatic PI3K Activation. PI. Kim Keppler-Noreuil, MD. ClinicalTrials.gov Identifier: NCT02428296 3. 15-DK-0174: Dynamic Post-Prandial Metabolism in Patients with Non-Alcoholic Fatty Liver Disease. PI. Yaron Rotman, MD. ClinicalTrials.gov Identifier: NCT02520609 Research highlights: 1. We published the results from 13-DK-0136, a single-site randomized crossover trial in collaboration with Dr. Monica Skarulis on the metabolic effects by an experimental melanocortin-4 receptor agonist in obese volunteers. Using the high sensitivity of the respiration chamber, we showed that a significant increase in resting energy expenditure (6.4%) and 24-hr fat oxidation was resulted from the experimental drug RM-493 (1mg/24hr) in twelve (6 male, 6 female) healthy obese adult study volunteers. This helps us further understand the role of melanocortin-4 plays in human energy metabolism. 2. We published two papers with Dr. Kevin Hall's group. One compared the changes in resting energy expenditure and body composition in obese subjects following massive weight loss achieved by bariatric surgery or calorie restriction plus vigorous exercise, and found that the latter group resulted in preservation of fat-free mass but resulted in greater metabolic adaption compared to the formal group. We further showed that metabolic adaption was related to the degree of energy imbalance and the changes in circulating leptin. In a more recent paper, we used the data we collected from the clinical protocol 09-DK-0081 to show that 6-day selected carbohydrate vs. fat restrictions (isocaloric matched 800 kcal/day) yielded a difference in fat oxidation (measured by the chamber studies) from the carbohydrate restriction; while a higher fat loss was also found in the fat restriction arm despite of no change in fat oxidation. The inclusion challenges the current view of low-carb dieting. 3. We recently published another paper with Dr. Jack Yanovski's group from NICHD (NCT01888939) that was a randomized crossover trial to examine sedentary behavior and metabolism in 28 normal-weight children (7- 11 years old). On two different days, the children either sat continuously for three hours or took 3-minute breaks to walk on a treadmill every half hour during that period. The study participants had their blood sugar and insulin levels tested before and after the experiment via the standard oral glucose tolerant tests. When children took breaks to walk, their blood sugar and insulin levels were lower than when they sat continuously. The findings indicate the childrens bodies were better able to maintain blood sugar levels when their sitting was interrupted. 4. We used the unique dataset that we collaborated with Icelandic Heart Association and NIA from 2008-2010, and published two papers in FY15. In a cohort of community-dwelling healthy older adult Icelandic volunteers (average age 80), we found that while day length and activity both had a significant influence on the pattern of sleep timing, the actual within-individual differences of the repeaters were rather subtle between periods of longer and shorter day-lengths. We conclude that the limited variation in sleep patterns and quality in response to significant changes in daylight may be due to long-term adaptation in these aging subjects. 5. The Core continues to support 19 clinical protocols and protocols from 5 different IC's of the NIH. Services rendered (FY15 activities): energy expenditure by whole-room respiratory chambers (311), resting energy expenditure by metabolic carts (169), graded-exercise tests (109), experimental food behavior tests (145), and body composition (209 DXA, 98 Bod Pod).