Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness.
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2022-05
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Rheumatoid arthritis (RA) T cells drive autoimmune features via metabolic reprogramming that reduces oxidative metabolism. Exercise training improves cardiorespiratory fitness (i.e., systemic oxidative metabolism) and thus may impact RA T cell oxidative metabolic function. In this pilot study of RA participants, we took advantage of heterogeneous responses to a high-intensity interval training (HIIT) exercise program to identify relationships between improvements in cardiorespiratory fitness with changes in peripheral T cell and skeletal muscle oxidative metabolism. In 12 previously sedentary persons with seropositive RA, maximal cardiopulmonary exercise tests, fasting blood, and vastus lateralis biopsies were obtained before and after 10 weeks of HIIT. Following HIIT, improvements in RA cardiorespiratory fitness were associated with changes in RA CD4 + T cell basal and maximal respiration and skeletal muscle carnitine acetyltransferase (CrAT) enzyme activity. Further, changes in CD4 + T cell respiration were associated with changes in naïve CD4 + CCR7 + CD45RA + T cells, muscle CrAT, and muscle medium-chain acylcarnitines and fat oxidation gene expression profiles. In summary, modulation of cardiorespiratory fitness and molecular markers of skeletal muscle oxidative metabolism during exercise training paralleled changes in T cell metabolism. Exercise training that improves RA cardiorespiratory fitness may therefore be valuable in managing pathologically related immune and muscle dysfunction.Trial registration: ClinicalTrials.gov, NCT02528344. Registered on 19 August 2015.
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Andonian, Brian J, Alec Koss, Timothy R Koves, Elizabeth R Hauser, Monica J Hubal, David M Pober, Janet M Lord, Nancie J MacIver, et al. (2022). Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness. Scientific reports, 12(1). p. 7450. 10.1038/s41598-022-11458-4 Retrieved from https://hdl.handle.net/10161/30453.
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Scholars@Duke
Brian Andonian
Timothy Robert Koves
My research is focused on 1) understanding metabolic perturbations that occur in subpopulations of skeletal muscle mitochondria in response to a chronic high lipid environment, 2) identifying specific metabolites of lipid-induced mitochondrial stress that contribute to skeletal muscle insulin resistance and type II diabetes, and 3) understanding how mitochondrial adaptations in response to exercise confer protection against lipid-induced mitochondrial dysfunction.
Elizabeth Rebecca Hauser
The incorporation of personalized medicine to all areas of human health represents a turning point for human genetics studies, a point at which the discoveries made have real implications for clinical medicine. It is important for students to gain experience in how human genetics studies are conducted and how results of those studies may be used. As a statistical geneticist and biostatistician my research interests are focused on developing and applying statistical methods to search for genes causing common human diseases. My research programs combine development and application of statistical methods for genetic studies, with a particular emphasis on understanding the joint effects of genes and environment.
These studies I work on cover diverse areas in biomedicine but are always collaborative, with the goal of bringing robust data science and statistical methods to the project. Collaborative studies include genetic and ‘omics studies of cardiovascular disease, health effects of air pollution, genetic analysis of adherence to an exercise program, genetic analysis in evaluating colon cancer risk, genetic analysis of suicide, and systems biology analysis of Gulf War Illness.
Keywords: human genetics, genetic association, gene mapping, genetic epidemiology, statistical genetics, biostatistics, cardiovascular disease, computational biology, diabetes, aging, colon cancer, colon polyps, kidney disease, Gulf War Illness, exercise behavior, suicide
Deborah Marie Muoio
Deb Muoio is professor in the Departments of Medicine and Pharmacology & Cancer Biology, George Barth Geller Distinguished Professor of Cardiovascular Disease, and Associate Director of the Duke Molecular Physiology Institute (DMPI). She is viewed nationally and internationally as a leader in the fields of diabetes, obesity, exercise physiology, and mitochondrial energy metabolism. Her laboratory investigates mechanisms of metabolic regulation, with emphasis on molecular events that link lifestyle factors such as over nutrition and physical inactivity to metabolic disorders, including obesity, diabetes, and heart failure. Her program features a translational approach that combines work in animal and cell-based models with human studies, using genetic engineering, molecular biology and mass spectrometry-based metabolomics and proteomics as tools to understand the interplay between mitochondrial physiology and cardiometabolic health. Her laboratory developed a sophisticated platform for deep and comprehensive assessment of mitochondrial bioenergetics and energy transduction. Her team is integrating this new platform with metabolomics, proteomics, and metabolic flux analysis to gain insights into mechanisms by which mitochondria modulate insulin action and metabolic resilience. She has published more than 120 papers in prominent journals such as Cell, Cell Metabolism, Circulation, Circulation Research, Diabetes, and JCI Insight. Dr. Muoio’s laboratory has enjoyed longstanding support from the NIDDK and NHLBI.
PhD, University of North Carolina, Chapel Hill, NC
William Erle Kraus
My training, expertise and research interests range from human integrative physiology and genetics to animal exercise models to cell culture models of skeletal muscle adaptation to mechanical stretch. I am trained clinically as an internist and preventive cardiologist, with particular expertise in preventive cardiology and cardiac rehabilitation. My research training spans molecular biology and cell culture, molecular genetics, and integrative human exercise physiology and metabolism. I practice as a preventive cardiologist with a focus on cardiometabolic risk and exercise physiology for older athletes. My research space has both a basic wet laboratory component and a human integrative physiology one.
One focus of our work is an integrative physiologic examination of exercise effects in human subjects in clinical studies of exercise training in normal individuals, in individuals at risk of disease (such as pre-diabetes and metabolic syndrome; STRRIDE), and in individuals with disease (such as coronary heart disease, congestive heart failure and cancer).
A second focus of my research group is exploration of genetic determinates of disease risk in human subjects. We conduct studies of early onset cardiovascular disease (GENECARD; CATHGEN), congestive heart failure (HF-ACTION), peripheral arterial disease (AMNESTI), and metabolic syndrome. We are exploring analytic models of predicting disease risk using established and innovative statistical methodology.
A third focus of my group’s work is to understand the cellular signaling mechanisms underlying the normal adaptive responses of skeletal muscle to physiologic stimuli, such as occur in exercise conditioning, and to understand the abnormal maladaptive responses that occur in response to pathophysiologic stimuli, such as occur in congestive heart failure, aging and prolonged exposure to microgravity.
Recently we have begun to investigate interactions of genes and lifestyle interventions on cardiometabolic outcomes. We have experience with clinical lifestyle intervention studies, particularly the contributions of genetic variants to interventions responses. We call this Lifestyle Medicopharmacogenetics.
KEY WORDS:
exercise, skeletal muscle, energy metabolism, cell signaling, gene expression, cell stretch, heart failure, aging, spaceflight, human genetics, early onset cardiovascular disease, lifestyle medicine
David Bruce Bartlett
David Bartlett is an Assistant Professor in the Department of Medicine, Division of Medical Oncology. He earned his PhD in Immunology from the University of Birmingham, England where he specialized in the effects of exercise and lifestyles on immune function and systemic inflammation in the elderly. He was awarded a coveted Marie Curie Outgoing Fellowship from the European Union which brought him to Duke under the guidance of William Kraus, MD where he assessed the immunological and physiological responses of exercise training in patients with prediabetes and rheumatoid arthritis. His laboratory studies the effects of exercise and energy balance on immune function and physiology of patient groups including cancer, arthritis and diabetes. His research program is focused on human studies employing a wide range of techniques including human physiological testing, exercise training to in vitro and ex vivo cellular assays.
Kim Marie Huffman
Determining the role of physical activity in modulating health outcomes (cardiovascular disease risk) in persons with rheumatologic diseases (rheumatoid arthritis, gout, osteoarthritis)
Integrating clinical rheumatology, basic immunology, metabolism, and exercise science in order to reduce morbidity in individuals with arthritis
Evaluating relationships between circulating and intra-muscular metabolic intermediates and insulin resistance in sedentary as well as individuals engaging in regular exercise
Addressing the role of physical activity in modulating inflammation, metabolism, and functional health in aging populations
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