Human Energy and Body Weight Regulation Core

研究重点： 1. 棕色脂肪组织作为一种潜在的增加能量消耗的来源继续引起我们的兴趣。与Celi博士合作，我们开发了一种新的分析技术，用于量化普通人类棕色脂肪感兴趣区域中2- 18F-FDG（18F-FDG）正电子发射断层扫描（PET）摄取水平的变化。我们还在我们的新方案（12-Dk-0097）中根据当前用于棕色脂肪活性检测的PET/CT金标准验证了该方法。我们发现，即使在控制了年龄、性别和其他参数之后，这也是非颤抖性产热的个体间变异性的重要贡献者。这项研究的意义表明，棕色脂肪的活动可能是一个重要的组成部分，非寒战产热和PET扫描可能是足够敏感，以量化其激活，这是上级传统的视觉检测。这些发现将在一份原始手稿中报告，该手稿目前正在由糖尿病杂志审查。 2. 内脏脂肪已被发现与各种心脏代谢疾病的危险因素显着相关。我们与iDXA扫描仪的制造商和GE Global Research合作，使用新开发和经验证的CoreScan分析功能，分离了我们在方案07-DK-0077中测量DXA身体成分的300多名异质受试者的内脏脂肪体积。初步研究结果表明，从简单DXA扫描中提取的内脏脂肪是可重复的，并且与BMI，腰围和常规DXA得出的总脂肪和区域脂肪百分比相比，是一些常见心脏代谢疾病风险生物标志物（如血脂谱，胰岛素敏感性指数）的更强预测因子。这些发现将在一份原始手稿中报告，该手稿现已提交给美国临床营养学杂志。 3. 在我们的积极参与下，2012财年启动了两项新协议。Chris Ramsden博士（NIAAA）已经开始了他的方案，标题为Omega-3 HUFA代谢的膳食必需脂肪酸调节;饱腹感和身体组成（11-AA-0028）。该方案的主要目标是研究欧米茄-3与欧米茄-6脂肪的饮食差异如何影响超重或肥胖女性的身体化学和激素水平，希望能够确定更好的饮食或治疗方法，以帮助人们达到并保持最佳健康体重。迄今为止，我们目前正在研究11个主题。Peter McGuire博士（NIGRI）已经开始了他的题为NIH UNI研究的方案：尿素循环障碍、营养与免疫（11-HG-0217），旨在描述观察到的营养和免疫缺陷，查询该患者人群中的营养/酶/免疫学相关性，描述该患者人群中的疫苗有效性，并在罕见的家族中寻找新的基因，这些家族有证据表明存在一种未知的尿素循环障碍。该人群将包括先前在NIH评估的患者、医生转诊和从clinicaltrials.gov以及国家尿素循环障碍基金会定向到该研究的家庭。该方案目前正在增加新的患者。 另外两个手稿是与校外合作者。 提供服务（FY 12活动）：全室呼吸室24小时能量消耗（265），代谢推车静息能量消耗（152），运动和身体功能测试（101），实验性饱腹感测试（79），身体成分（222 DXA，324 Bod Pod），肌肉活检（47），皮下脂肪活检（23），健康和体格检查（76）。

Research highlights: 1. Brown adipose tissue continues to interest us as a potential source of increase energy expenditure non-pharmacologically. In collaboration with Dr. Celi, we have developed a new analytical technique to quantify the changes in the level of uptake 2-18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) in the region of interest of common human brown fat. We have also validated this method against the current gold-standard of PET/CT for brown fat activity detection in our new protocol (12-Dk-0097). We found that to be a significant contributor to the inter-individual variability of non-shivering thermogenesis, even after controlling for age, gender, and other parameter. The implication of this study showed that brown fat activity may be an important component of non-shiver thermogenesis and PET scans may be sensitive enough to quantify its activation, which is superior to the traditionally visual detection. These findings will be reported in an original manuscript which is now under review by the Journal Diabetes. 2. Visceral fat has been found to correlate significantly with various cardiometabolic disease risk factors. We have collaborated with the manufacturer of the iDXA scanner and GE Global Research, using the newly-developed and validated CoreScan analysis capabilities to isolate the visceral fat volume in over 300 of the heterogeneous subjects we measured DXA body composition in the protocol 07-DK-0077. Preliminary findings suggest that visceral fat extracted from the simple DXA scans are reproducible, and is a stronger predictor of some common cardiometabolic disease risk biomarkers such as lipid profiles, insulin sensitivity index, when compared to BMI, waist circumferences, and conventionally DXA derived total and regional percent fat. These findings will be reported in an original manuscript which is now being submitted to American Journal of Clinical Nutrition. 3. Two new protocols have started in FY 2012 with our active involvements. Dr. Chris Ramsden (NIAAA) has started his protocol titled Dietary Essential Fatty Acid Regulation of Omega-3 HUFA Metabolism; Satiety and Body Composition (11-AA-0028). The main goal of this protocol is to study how diets differ in Omega-3 vs. Omega-6 fat affect body chemistry and hormone levels in women who are overweight or obese, with hope to be able to determine better diets or treatments to help people reach and maintain an optimum healthy weight. We are currently studying 11 subjects to date. Dr. Peter McGuire (NIGRI) has started his protocol titled The NIH UNI Study: Urea Cycle Disorders, Nutrition and Immunity (11-HG-0217), which aims to describe the nutritional and immune deficiencies seen, query for nutrition/enzymatic/immunologic correlations in this patient population, describe vaccine efficacy in this patient population, and search for new genes in rare families that have evidence for an unknown class of urea cycle disorder. The population will consist of patients previously evaluated at NIH, physician referrals, and families directed to the study from clinicaltrials.gov as well as the National Urea Cycle Disorders Foundation. This protocol is currently accruing new patients. Two other manuscripts were with extramural collaborators. Services rendered (FY12 activities): 24-hr energy expenditure by whole-room respiratory chambers (265), resting energy expenditure by metabolic carts (152), exercise and physical function testing (101), experimental satiety test (79), body composition (222 DXA, 324 Bod Pod), muscle biopsies (47), subcutaneous fat biopsies (23), and Health and Physical Exams (76).