Human Energy and Body Weight Regulation Core

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

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 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 significantly impacted the MCRU, our census is still slowly recovering: energy expenditure by respiratory chambers (55), resting energy expenditure by metabolic carts (86), experimental food behavior tests (27), and body composition (71 DXA). The Core currently support 23 clinical protocols and protocols from 14 different IC's of the NIH. Selected research highlights in FY22: 1. We are supporting 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 18 participants, completed 5, and following 12. In FY22, we also started the Natural history of post-coronavirus disease 19 convalescence at the NIH study (NCT04573062) 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. We are moving towards a deep phenotyping protocol similar to the ME/CFS that we have completed, with a repeated metabolic chamber overnight study in FY23. 2. We collaborated with Dr. Rebecca Brown of the NIDDK on two publications in FY22. Gluconeogenesis is an energy-requiring process that is upregulated in diabetes, contributing to hyperglycemia. Previous studies have estimated that gluconeogenesis accounts for less than 10% of resting energy expenditure. In a paper published in Am J Physiol Endo Metab, we estimated that the energy expenditure attributable to gluconeogenesis in uncommon and severe forms of insulin resistance and common, milder forms of insulin resistance. In these populations, gluconeogenesis accounts for almost one-third of resting energy expenditure, substantially higher than previously theorized in the literature. In another study, we found that leptin (Metreleptin) therapy initiation decreased energy expenditure (EE) in patients with lipodystrophy, but no changes were observed after metreleptin withdrawal. Thyroid hormone was higher on metreleptin in both initiation and withdrawal cohorts. Decreased EE after metreleptin in lipodystrophy may result from reductions in energy-requiring metabolic processes that counteract increases in EE via adipose tissue-specific neuroendocrine and adrenergic signaling.