Human Energy and Body Weight Regulation Core

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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. Due to the COVID-19 global pandemic that closed the MCRU on March 15, only to gradually returning in limited capacity starting in July. As a result, our census and services rendered were negatively impacted: energy expenditure by respiratory chambers (91), resting energy expenditure by metabolic carts (112), graded-exercise tests (27), experimental food behavior tests (237), and body composition (101 DXA, 15 Bod Pod). The Core continues to support 29 clinical protocols and protocols from 14 different IC's of the NIH. We are planning to begin several new clinical protocols in late 2020 to early 2021 (if the MRCU is back to normal operational status), including an exercise intervention trial in post-hospitalized COVID patients (with NIH Clinical Center Rehabilitation Department), a protocol to test anti-Inflammatory effects of time-restricted feeding in patients with inflammatory psoriasis (with NHLBI), a pilot study to measure acute effects of medium chain triglyceride nutritional ketosis on Parkinsons Disease symptoms and biomarkers (with NIMH), another study with NIMH to measure sleep, energy expenditure, and circadian rhythm in patients with bipolar disorders, and a randomized clinical trial to measure early metabolic effects of two new anti-HIV drug combinations in healthy volunteers. Research highlights in FY20: 1. There are currently more than 30 research laboratories on 5 continents which have whole-room indirect calorimeters for human metabolism studies. The types of studies range from comparison of respiratory calorimetry measures across populations to use for assessment of exercise physiology, activity monitoring, sleep, and effects of diet and pharmacologic and environmental interventions. The limited availability is due to expense and the technical expertise required to support their operation and continued maintenance. However, there are currently no accepted standards for calibration and operation, quality control, protocol design, signal processing, or data reporting. As a result, comparing results between laboratories is often difficult, and the ability to perform multicenter trials is limited. We organized and lead an international panel of room indirect calorimeter experts from the US, Europe, and Asia from 2019-20 with the goal to establish the standards for reporting 1) technical specifications; 2) data reduction, and analytical approaches; 3) performance standards including accuracy, precision, stability, and repeatability; 4) elements of study design, including the basis for power analyses, inclusion/exclusion criteria, and appropriate considerations of potential confounders (e.g., pre-study dietary intake); and 5) outcome measures. The panel agreed this effort would improve the ability to compare data among studies, educate and guide new researchers to the field, and facilitate preparations and reviews of new publications. The manuscript outlining the Room Indirect Calorimetry Operating and Reporting Standards, version 1.0 (RICORS 1.0) provides guidance to ensure consistency and facilitate meaningful comparisons and reproducibility of human energy metabolism studies across publications and clinical sites. It is published and chosen as the Editors Choice selection in the 2020 September issue of Obesity. 2. We published several papers in FY 20 on the changes of sleep and physical activity patterns and their associations with mental and physical health parameters in Icelandic adolescents at 15 and 17 years of age, all stemming from a long-term collaboration project with a team of researchers at the University of Iceland. We found an alarming percentage of these adolescents did not have sufficient sleep during most school nights (averaging about 6 hours/night), and screen time was associated with the sleep variability, which together with physical inactivity, were associated with less favorable metabolic profiles such as total and trunk fat percentages. Together, these findings support the idea that both sufficient amount of sleep, physical activity, and perhaps regular schedules are important for the health of adolescents. 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 and Dr. Lauren Shomaker (previously a postdoc with Dr. Yanovski, now an associate professor at Colorado State University) and publish results in the area of adolescent weight and insulin resistance and depression. For example, we found that, in adolescent girls at-risk for T2D with moderately elevated depression, randomization to cognitive-behavioral therapy (CBT) produced greater decreases in depression at post-treatment and greater decreases in fasting/2-h insulin at 1 year, compared to health education. We then examined whether decreasing depression explained intervention effects on body composition and insulin outcomes and found an indirect effect of CBT on decreased 1-year fasting insulin via decreases in depression during treatment, among adolescents with more elevated baseline depression. These findings suggest that insulin resistance and anxiety symptoms are associated and decreasing elevated depression may be one mechanism in the targeted prevention of T2D in at-risk adolescents.