Development of obesity and metabolic clinical research programs

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For the first aim, we have made progress in the following areas. 1. Indirect calorimeters are recognized as the gold-standard measurement of the components of energy expenditure (sleeping, resting, postprandial, exercise, and recovery). Together with Dr. Brychta (PhD in Biomedical Engineering), we have systematically modified our 3-room whole-room indirect calorimetry chamber system in the past 4 years, such that we achieve not only precision, responsiveness, and accuracy, but also reliability, consistency, and efficiency. Specifically, we have dramatically reduced the environmental influences on the performance of the system (such as building humidity and electrical power fluctuations). Our expertise in chamber design and operations has been recognized by US and International researchers. With three other experts in US and Europe, I co-organized the 2nd international conference on Recent Advances and Controversies in Measuring Energy Metabolism (Nov 2-4, Maastricht, The Netherlands), where Dr. Brychta and I gave an oral presentation and a plenary talk, respectively. 2. For accurate free-living physical activity measurements, portable accelerometers are the gold-standard objective technique. Building on the foundation of our previous work in this fast-developing area (Chen et al. 2012), we are continuing our collaborations with several groups here at the NIH and globally. In FY 2011, we have evaluated the technical performance and reliability of a newly developed accelerometer to be implemented in the National Health and Nutrition Examination Survey (NHANES 2011-12) study. In FY 2012, the field application (more than 7000 person-weeks have been collected to date) has shown significantly more compliance from test subjects and more detailed physical activity data as compared to the previous NHANES accelerometer study (2005-06). We have completed a follow-up thorough technical evaluation of the accelerometers after multiple use to confirm that the sensitivity and the inter-monitor variability has not deviated from new monitors. This is an important finding to ensure the continuity and comparability of the NHANES study and for other longitudinal studies that use these monitors repeatedly over years. The finding of this study has been submitted in a manuscript for American Journal of Epidemiology. Other collaborations have also resulted in four published manuscripts. For the second aim, we made progress in the following areas: 1. In FY 2012, our new clinical protocol titled Energy expenditure responses to a range of environmental temperatures around the thermal neutral zone (12-DK-0097) was approved by scientific reviewers and NIDDK IRB (in April 2012). The rationale is to improve our understanding of human dynamic regulation of energy expenditure in response to subtle changes in environmental temperature. In particular, the ongoing research on brown adipose tissue and its role in non-shivering thermogensis in our and other labs have generated substantial interests in the field of energy metabolism and obesity. To date, we have studied seven (7) healthy lean volunteers (21.64.6 yrs, BMI 23.31.6 kg/m2, and %fat by DXA 18.72.8%). We measured resting energy expenditure in a 5-hour period in the room calorimeter with randomized environmental temperature ranging between 16C and 31C, in 10-13 consecutive days (a 2-week inpatient protocol). We also carefully measured potential shivering by surface electromyography (EMG), acceleration, and heart rate, skin and core body temperatures, and stress responses by blood and urinary markers, while controlling for physical activity, clothing, posture, and dietary intake. Preliminary results have shown that we have developed a sensitive and reproducible measurement protocol to quantify cold-induced thermogenesis and its associated physiological responses. Moreover, we can now confidently quantify the resting EE in the thermal neutral zone (TNZ), detect shivering onset with EMG, the slope and the maximum capacity of non-shivering thermogenesis, all of which are helping us to understand the normal shape and individual variability of EE vs. environmental temperature curve in this elemental human physiology. The preliminary findings have revealed a higher maximum non-shivering theremogenesis and a wider shivering threshold inter-individual variability in these individuals than we originally hypothesized. 2. We are now moving towards our second (and primary) study aim to study the influence of obesity in human non-shivering thermogenesis. We are now actively recruiting our next cohort of patients who are between the BMI of 30-40 kg/m2 and otherwise healthy. By using the same protocol, we will compare the parameters that define the shape of the TNZ, shivering threshold, and the slope and the maximum capacity of non-shivering thermogenesis between obese and lean young males.