2021 DIG Research Project | “Heme Oxygenase-1 Regulation of Skeletal Muscle Inflammation and Mitochondrial Fitness in Sarcopenic Obesity”
Heath Gasier, PhD, RD, is a physiologist and assistant professor within Duke Anesthesiology’s Center for Hyperbaric Medicine and Environmental Physiology (CHMEP). His research interests include diving and altitude physiology, nutrition and bone health, and skeletal muscle mitochondrial dynamic regulation in stress. He is a member of the American College of Sports Medicine and the American Physiological Society, and has been a registered dietitian since 2001.
Gasier enlisted into the US Navy after graduating from high school in NE Ohio. He later earned a BSAS in nutrition from Youngstown State University and an MS in nutrition from Case Western Reserve University. In addition, he completed a dietetic internship from University Hospitals Cleveland Medical Center. As a commissioned US Air Force officer, he served as a clinical dietitian at Wilford Hall Medical Center. Heath was awarded a US Navy Health Services Collegiate Program Scholarship to complete a PhD in exercise physiology from Texas A&M University. His area of study was skeletal muscle biology with a focus on in vivo muscle protein synthesis. Upon graduation, he was assigned to the Naval Submarine Medical Research Laboratory as a naval research physiologist. During this time, he served as a principal investigator on research projects directed towards understanding the impact of prolonged submergence on bone and metabolic health, diving and oxidative stress, and the efficacy of nitrates on improving blood flow and muscular performance at high altitude. He also served as an assistant department head and vice chair of scientific review, and scientific integrity officer. Gasier was awarded an out-of-service fellowship in hyperbaric physiology at the Duke CHMEP under the direction of Dr. Claude Piantadosi. During this time, he conducted investigations with Dr. Ivan Demchenko that were focused on identifying the location and mechanisms of oxygen-induced seizures, and the use of antiepileptic drugs to delay seizure onset. He was then assigned to the Uniformed Services University of the Health Sciences as an assistant professor in the Department of Military and Emergency Medicine. There, he began a line of research that was aimed at understanding how heat stress and nutrient excess induced oxidant production influences skeletal muscle mitochondrial dynamic regulation and function. In addition, he performed investigations that were designed to test whether carbon monoxide could preserve bone and skeletal muscle mitochondrial fitness in diet-induced obesity. Gasier served as the director of animal research within the Consortium of Health and Military Performance (CHAMP), and course director of “Warfighter and the Environment” and “Military Field Practicum 101.” He also served as the Navy’s representative for the Department of Defense’s Military and Operational Medicine Nutrition and Dietary Supplement expert panel. In 2019, Gasier retired from military service and returned to the CHMEP with the goal of continuing his research under the mentorship of Drs. Piantadosi and Richard Moon.
Sarcopenia and obesity are conditions whereby oxidative damage and low-grade inflammation are linked to impaired mitochondrial quality control and function. Heme oxygenase-1 (HO-1) induction reduces skeletal muscle oxidant production and inflammation in diet-induce obesity and models of skeletal muscle atrophy. HO-1 is an enzyme system that catalyzes the breakdown of heme, an iron-containing porphyrin and prooxidant, to bilverdin, non-heme iron and carbon monoxide (CO). Bilverdin is rapidly reduced to bilirubin via biliverdin reductase (an antioxidant), and non-heme iron is either stored as ferritin or oxidized by hydrogen peroxide forming oxidants (Fenton reaction). CO is a gas signaling molecule that regulates activation of the transcription factors nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear respiratory factor (NRF)-1 and NRF-2, which coordinately activate antioxidant and inflammatory gene transcription. In addition, HO-1/CO mediated activation of Nrf2 and NRF-1 regulates mitochondrial quality control, the integrated processes of mitochondrial dynamics, mitophagy and biogenesis. It remains unknown whether the skeletal muscle HO-1 enzyme system is impacted in sarcopenic obesity, and contributing to deterioration in mitochondrial population and muscle atrophy.
DREAM Innovation Grants (DIG) support innovative high-risk and potentially high-reward investigations to accelerate anesthesia and pain management research and are made possible through Duke Anesthesiology’s Duke DREAM Campaign. Gasier is excited to have received a 2021 DIG, and expects to generate preliminary data for a more focused, pre-clinical RO1 proposal that is directed towards understanding how the HO-1/CO system regulates cell stress in sarcopenic obesity during illness. This work is supportive of his long-term goal of discovering novel strategies for preserving skeletal muscle mass and metabolic health in obesity and aging.