Human Energy and Body Weight Regulation Core

人体能量和体重调节核心

• 批准号: 10008864
• 负责人: Kong Chen
• 金额: $ 35.35万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10008864
• 关键词: Accounting; Adolescence; Adolescent obesity; Adult; Affect; Benefits and Risks; Biomedical Research; Body Composition; Body Temperature; Body Weight; Body Weight Changes; Calories; Calorimetry; Carbohydrates; Cardiovascular Diseases; Censuses; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Colchicine; Consumption; Custom; Data; Data Analyses; Development; Diabetes Mellitus; Diet; Dimensions; Dose; Dual-Energy X-Ray Absorptiometry; Energy Intake; Energy Metabolism; Enrollment; Evaluation; Exercise stress test; Exertion; Fatty acid glycerol esters; Fiber; Food; Health; Heart Rate; Human; Individual; Inflammatory; Inpatients; Insulin Resistance; Intake; Length of Stay; Macronutrients Nutrition; Malignant Neoplasms; Measurement; Measures; Mental Depression; Metabolic; Metabolic syndrome; Metabolism; Modification; Multicenter Trials; National Human Genome Research Institute; National Institute of Child Health and Human Development; OGTT; Obesity; Obesity Epidemic; Outcome; Outpatients; Overweight; PIK3CA gene; Paper; Participant; Patient Self-Report; Patients; Physical Fitness; Physical activity; Physiology; Placebos; Population; Process; Randomized; Randomized Controlled Trials; Regulation; Research; Research Design; Research Institute; Rest; Risk; Running; Safety; Services; Sirolimus; Site; Sodium; Strategic Planning; Tissues; Translational Research; United States National Institutes of Health; Universities; Walking; Weight; Youth; adult obesity; analytical method; anxiety symptoms; associated symptom; behavior test; design; energy balance; energy density; fitness; improved; instrument; insulin sensitivity; ketogenic diet; mTOR Inhibitor; middle age; obesity in children; obesity prevention; obesity treatment; open label; portability; primary outcome; respiratory; side effect; sugar

The Core continues to be a part of the Metabolic Clinical Research Unit (MCRU), which was established at NIH in 2007 under the first NIH Strategic Plan for Obesity Research (http://www.obesityresearch.nih.gov/strategic-plan). It is design to conduct research to identify potential causes and evaluate treatments of obesity. Currently 1/3 of the adult US population is obese and another 1/3 are overweight. Obesity is a major cause of diabetes, cardiovascular disease, and some cancers, yet our understanding of obesity physiology is rudimentary. The obesity epidemic has continued unabatedthe need for rigorous and properly controlled metabolic research is even more important. At the NIH, much of the Intramural clinical research is conducted on the MCRU that consists of the 5SW-N (inpatient) unit, 5SW-S (day hospital), and 7SW-S whole room calorimetry suites, which includes a special room with a DXA body composition scanner, and Bod Pod, an exercise testing room, portable activity measurements, and highlighted by the three customized whole-room indirect calorimeters (respiratory chambers) as the key components of the Core function. Despite of the Clinical Centers decision to reduce the 5SW-N inpatient unit from 10 to 7 rooms at the beginning of FY19, we actually increased our census and the services rendered: energy expenditure by respiratory chambers (383), resting energy expenditure by metabolic carts (551), graded-exercise tests (78), experimental food behavior tests (677), and body composition (233 DXA, 51 Bod Pod). The Core continues to support 29 clinical protocols and protocols from 14 different IC's of the NIH. Research highlights in FY19: 1. With Dr. Kevin Hall, we investigated whether ultra-processed foods affect energy intake in 20 weight-stable young to middle-aged adults. Subjects were randomized to receive either ultra-processed or unprocessed diets for 2 weeks immediately followed by the alternate diet for 2 weeks as inpatients on our Unit. Meals were designed to be matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Energy intake was greater during the ultra-processed diet (508 106 kcal/day; p = 0.0001), with increased consumption of carbohydrate (280 54 kcal/day; p < 0.0001) and fat (230 53 kcal/day; p = 0.0004), but not protein (-2 12 kcal/day; p = 0.85). Weight changes were highly correlated with energy intake (r = 0.8, p < 0.0001), with participants gaining 0.9 0.3 kg (p = 0.009) during the ultra-processed diet and losing 0.9 0.3 kg (p = 0.007) during the unprocessed diet. The data suggest that limiting consumption of ultra-processed foods, as least in the short-term, may be an effective strategy for obesity prevention and treatment. 2. Using data we collected from a multi-center trial with Pennington Biomedical Research Center, Columbia University, the Translational Research Institute for Metabolism and Diabetes, we examined energy expenditure differences between isocaloric diets varying widely in carbohydrate (4 weeks inpatient with isocaloric ketogenic diet, KD, or baseline diet BD) and to quantitatively compare DLW data with respiratory chamber and body composition measurements within an energy balance framework. Neither chamber EE nor EE using energy balance (controlled intake and body composition) were different between KD and BD, but DLW EE was 209 83 kcal/d higher during the KD (P = 0.023) but was not significantly increased when adjusted for energy balance (EEDLWRQ = 139 89 kcal/d; P = 0.14). The data suggest that DLW calculations failing to account for diet-specific energy imbalance effects on RQ erroneously suggest that low-carbohydrate diets substantially increase energy expenditure. 3. We have been studying childhood obesity since the establishment of the Core. We continue to contribute to the studies with Dr. Jack Yanovskis research group from NICHD. In several recent papers, we sought to determine the relationship of physical fitness with two developmental phenomena of adolescence, insulin resistance and depression/anxiety symptoms among at-risk youth. We analyzed data from 241 overweight or obese adolescents (1217 years) from two studies conducted on our Unit. Insulin sensitivity (oral glucose tolerance test) was positively associated with fitness by walk/run distance (p<0.01), even after accounting for all covariates. Self-reported anxiety symptoms were inversely related to perceived exertion (p<0.05), adjusting for covariates. These findings suggest that insulin resistance and anxiety symptoms are associated with different dimensions of physical fitness in overweight or obese adolescents and could both potentially contribute to declining fitness and worsening metabolic outcomes in at-risk youth. 4. We also supported Drs. Andrew Demidowich and Jack Yanovski in a pilot randomized controlled trial to evaluate the efficacy and safety of colchicine (0.6 mg vs. placebo for 3 months) for improving metabolic and inflammatory outcomes in people with obesity and metabolic syndrome (MetS). Of 40 adult study participants randomized, 37 completed the trial. We found colchicine significantly improved obesity-associated inflammatory variables and showed a good safety profile among adults with obesity and MetS who did not have diabetes. These results suggest a larger, adequately powered study should be conducted to determine whether colchicine improves insulin resistance and other measures of metabolic health in at-risk individuals. 5. We collaborated in a NHGRI clinical trial in treating patients with PIK3CA-related overgrowth spectrum (PROS) with an mTOR inhibitor sirolimus. Thirty-nine patients with confirmed PROS and progressive overgrowth were enrolled into open-label studies across three centers. The a priori primary outcome was affected vs unaffected regional body composition changes assessed using dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy. Thirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of -7.2% (p=0.04) at affected sites, but not at unaffected sites (+1.7%, p=0.48). This study suggests that low-dose sirolimus can modestly reduce overgrowth, but cautions that the side-effect profile is significant, mandating individualized risk-benefit evaluations for sirolimus treatment in PROS.

该核心仍然是代谢临床研究单位 (MCRU) 的一部分，该单位于 2007 年根据第一个 NIH 肥胖研究战略计划在 NIH 成立 (http://www.obesityresearch.nih.gov/strategic-plan) 。它的目的是进行研究，以确定肥胖的潜在原因并评估肥胖的治疗方法。 目前，1/3 的美国成年人口肥胖，另有 1/3 超重。肥胖是糖尿病、心血管疾病和一些癌症的主要原因，但我们对肥胖生理学的了解还很初级。 肥胖症的流行有增无减，因此更需要严格且适当控制的代谢研究。在 NIH，大部分校内临床研究都是在 MCRU 上进行，该 MCRU 由 5SW-N（住院）单元、5SW-S（日间医院）和 7SW-S 全室量热套件组成，其中包括一个特殊房间，配备DXA 身体成分扫描仪、Bod Pod、运动测试室、便携式活动测量，并以三个定制的全室间接热量计（呼吸室）作为该系统的关键组件。核心功能。尽管临床中心决定在 2019 财年年初将 5SW-N 住院病房从 10 个房间减少到 7 个房间，但我们实际上增加了普查和提供的服务：呼吸室的能量消耗 (383)、代谢车的静息能量消耗(551)、分级运动测试 (78)、实验性食物行为测试 (677) 和身体成分 (233 DXA、51 Bod Pod)。该核心继续支持 29 种临床协议以及来自 NIH 14 个不同 IC 的协议。 2019 财年研究亮点： 1. 我们与 Kevin Hall 博士合作，调查了超加工食品是否会影响 20 名体重稳定的年轻至中年成年人的能量摄入。受试者被随机分配接受超加工或未加工饮食 2 周，随后作为我们科室的住院患者接受替代饮食 2 周。膳食的设计要与所提供的卡路里、能量密度、常量营养素、糖、钠和纤维相匹配。受试者被指示根据需要食用尽可能多或尽可能少的食物。超加工饮食期间的能量摄入量更高（508 106 kcal/天；p = 0.0001），碳水化合物（280 54 kcal/天；p < 0.0001）和脂肪（230 53 kcal/天；p = 0.0004）消耗量增加），但不是蛋白质（-2 12 kcal/天；p = 0.85）。体重变化与能量摄入高度相关（r = 0.8，p < 0.0001），参与者在超加工饮食期间体重增加了 0.9 - 0.3 公斤（p = 0.009），而在未加工饮食期间体重减轻了 0.9 - 0.3 公斤（p = 0.007）。数据表明，限制超加工食品的消费（至少在短期内）可能是预防和治疗肥胖的有效策略。 2. 使用我们与哥伦比亚大学彭宁顿生物医学研究中心、代谢和糖尿病转化研究所进行的多中心试验收集的数据，我们检查了碳水化合物差异很大的等热量饮食之间的能量消耗差异（住院4周等热量生酮饮食的患者） 、KD 或基线饮食 BD），并在能量平衡框架内将 DLW 数据与呼吸室和身体成分测量值进行定量比较。 KD 和 BD 之间使用能量平衡（控制摄入量和身体成分）的室 EE 和 EE 均无差异，但 KD 期间 DLW EE 增加了 209 83 kcal/d (P = 0.023)，但在调整能量平衡后并未显着增加（EEDLWRQ = 139·89 kcal/d；P = 0.14）。数据表明，DLW 计算未能考虑饮食特定的能量不平衡对 RQ 的影响，错误地表明低碳水化合物饮食会大幅增加能量消耗。 3. 自核心成立以来，我们一直在研究儿童肥胖问题。我们继续与 NICHD 的 Jack Yanovskis 博士研究小组一起为研究做出贡献。在最近的几篇论文中，我们试图确定身体健康与青春期两种发育现象（胰岛素抵抗和高危青少年抑郁/焦虑症状）之间的关系。我们分析了我们单位进行的两项研究中 241 名超重或肥胖青少年（1217 岁）的数据。即使考虑了所有协变量，胰岛素敏感性（口服葡萄糖耐量测试）与步行/跑步距离的健康度呈正相关（p<0.01）。自我报告的焦虑症状与感知的用力呈负相关（p <0.05），调整协变量。这些发现表明，胰岛素抵抗和焦虑症状与超重或肥胖青少年的不同身体健康维度相关，并且可能导致高危青少年的健康状况下降和代谢结果恶化。 4. 我们也支持Drs。 Andrew Demidowich 和 Jack Yanovski 进行了一项随机对照试验，旨在评估秋水仙碱（0.6 毫克与安慰剂 3 个月）改善肥胖和代谢综合征 (MetS) 患者代谢和炎症结果的功效和安全性。 40 名成人研究参与者被随机分配，其中 37 人完成了试验。我们发现秋水仙碱显着改善了与肥胖相关的炎症变量，并且在没有糖尿病的肥胖和代谢综合征成人中显示出良好的安全性。这些结果表明，应该进行更大规模、更有力的研究，以确定秋水仙碱是否可以改善高危个体的胰岛素抵抗和代谢健康的其他指标。 5. 我们在 NHGRI 临床试验中合作，使用 mTOR 抑制剂西罗莫司治疗 PIK3CA 相关过度生长谱 (PROS) 患者。 39 名确诊为 PROS 且进行性过度生长的患者被纳入三个中心的开放标签研究。先验主要结果是在 26 周未经治疗的磨合期和 26 周西罗莫司治疗期间使用双能 X 射线吸收测定法评估受影响与未受影响的区域身体成分变化。三十名参与者完成了这项研究。西罗莫司导致受影响部位的平均总组织体积百分比变化为-7.2%（p=0.04），但未受影响部位则没有变化（+1.7%，p=0.48）。这项研究表明，低剂量西罗莫司可以适度减少过度生长，但警告说，副作用很大，需要对 PROS 中的西罗莫司治疗进行个体化风险效益评估。