Human Energy and Body Weight Regulation Core

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications & trials

Abstract

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 unabated the 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. The impacts of COVID-19 are still being felt by the MCRU, the CORE, and the clinical research program as a whole. Study recruitments in all protocols are still slowly recovering. The NIH Clinical Center pharmacy is particularly impacted for any studies needing interventional drugs or tracers. In addition, the temperature control to our three whole-room indirect calorimeters has been malfunctioning routinely with large temperature fluctuations reaching 10C beyond the setpoints. After multiple failed attempts to mitigate this problem with the NIH Office of Research Facilities, we made the decision to build our own temperature control system for two of the three rooms. In FY23, we were forced to converted them to a separate temperature control system from the central building system. We have also experienced other issues with the building medical air supply and power outages and fluctuations, thus we are designing an independent medical air system for our room calorimeters in FY24. Research activities: energy expenditure by respiratory chambers (181), resting energy expenditure by metabolic carts (256), experimental food behavior tests (50), and body composition (301). The Core currently support 31 active clinical protocols from 14 IC's of the NIH. Selected research highlights in FY22: 1. We continue to support two major NIH Clinical Center studies on COVID-19: the chronic adaptation and response to exercise trial (COVID-CARE https://clinicaltrials.gov/ct2/show/NCT04595773) initialized in Oct 2020. The primary objective of the trial is to study if participation in a rehabilitation exercise program can help people recovering from COVID-19. Eventually 80 adults ages 18-80 with confirmed SARS-CoV2 infection with clinical symptoms will be studied. This randomized controlled trial will determine whether aerobic exercise training has a beneficial effect on physical function, health-related quality of life, free-living physical activity and sleep quality among survivors of COVID-19 (our primary responsibility). Participants will be randomized to either an aerobic exercise training and education (AET+) group or a control education only group (CON) for 10 weeks. Assessments for physical function, self-reported health outcomes for quality of life (QOL), free-living physical activity and sleep quality will be measured at baseline and following the 10-week intervention period. Participants in the CON group will then crossover and perform AET after the 10-week follow-up visit. All participants will be monitored for one year to capture free-living physical activity, sleep quality and health-related QOL outcomes over time. It is hypothesized that following 10 weeks, physical function, health-related QOL, free-living physical activity and sleep quality will show greater improvement with AET+. To date, we have enrolled 42 participants, completed 32, and following 21 (quarterly and annual visits). In FY23, we continue to be the "home" clinical unit to house and study participants in the Natural history of post-coronavirus disease 19 convalescence at the NIH study (NCT04573062). It is designed to define the range and timing of symptoms that people have before, during, and after COVID-19 infection. We are conducting the second phase of the inpatient studies on the MCRU with several components of metabolic health including resting EE, body composition, and wrist actigraphy. To date, we have enrolled 22 participants to the MCRU. We are moving towards a deep phenotyping protocol similar to the ME/CFS that we have completed, with a repeated metabolic chamber overnight study starting in FY24. 2. We collaborated with Dr. Rotman from the Liver Disease Branch of the NIDDK on a study on nonalcoholic fatty liver disease (NAFLD) where we tested hypothesized the existence of a unique postprandial alterations in hepatic lipid metabolism. 37 patients with NAFLD and 10 healthy control subjects ingested a standardized liquid meal with pre- and postprandial blood sampling. Postprandial plasma lipid kinetics were characterized at the molecular lipid species level by untargeted lipidomics, cluster analysis. There was a specific increase of multiple plasma diacylglycerol (DAG) species at 4 hours postprandially (studied in our chambers) in patients with NAFLD but not in controls. The increase in plasma DAGs appears early in the disease course, is dissociated from NAFLD severity and obesity, and correlates with postprandial insulin levels. In doing so, we identified a selective insulin-related increase in hepatic secretion of endogenously derived DAGs after a mixed meal as a unique feature of NAFLD. DAGs are known to be lipotoxic and associated with atherosclerosis. Although it is still unknown whether the increased exposure to hepatic DAGs contributes to extrahepatic manifestations and cardiovascular risk in NAFLD, our study highlights the importance of extending NAFLD research beyond the fasting state.