Human Energy and Body Weight Regulation Core

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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).