Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness

Abstract

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.

Effect of Remotely Supervised Weight Loss and Exercise Training Versus Lifestyle Counseling on Cardiovascular Risk and Clinical Outcomes in Older Adults With Rheumatoid Arthritis: A Randomized Controlled Trial

“… 26 Overall, cardiorespiratory fitness improvements were associated with positive changes in RA peripheral CD4+ T cell oxidative metabolism. 27 In sum, our previous findings highlight the potential for exercise training to impact clinical outcomes by targeting systemic and tissue‐specific metabolism, especially in older patients with RA. In the present study, we sought to further evaluate the effects of exercise, in combination with weight loss through diet modification, on cardiovascular health, disease activity, and patient‐reported outcomes in a population of patients with RA at high risk for cardiometabolic dysfunction.…”

“…In fact, improvements in RA disease activity were greatest in older age participants with high erythrocyte sedimentation rate (ESR), low cardiorespiratory fitness, and altered baseline skeletal muscle‐specific metabolism 26 . Overall, cardiorespiratory fitness improvements were associated with positive changes in RA peripheral CD4+ T cell oxidative metabolism 27 . In sum, our previous findings highlight the potential for exercise training to impact clinical outcomes by targeting systemic and tissue‐specific metabolism, especially in older patients with RA.…”

Rheumatoid arthritis and cardiovascular comorbidities

“…Decreased cardiorespiratory fitness [as measured by relative oxygen consumption (VO2) peak] is a strong predictor of CVD and overall mortality. Improvement in cardiorespiratory fitness in RA patients with high intensity interval training (HITT) was reported to be associated with increase in the amount of antiinflammatory cytokine IL-10 [185] and decrease in galectin-3, a marker of chronic inflammation and CVD risk [186]. A pilot study of 12 seropositive RA patients concluded that exercise induced improvements in the cardiorespiratory fitness and molecular markers of skeletal muscle oxidative metabolism were associated with changes in T cell metabolism which raises the question of whether exercise training, possibly through adaptations in skeletal muscle, can improve immune dysfunction [187].…”

Роль Фізичних Вправ У Реабілітації Хворих На Ревматоїдний Артрит

“…Оскільки зниження кардіореспіраторної витривалості є одним з найсильніших предикторів серцево-судинних захворювань та смертності від усіх причин, лікування РА вимагає розриву порочного кола, яке пов'язує відсутність фізичної активності з порушенням окисного метаболізму [2]. Так показано, що високоінтенсивні інтервальні тренування (ВІТ) -однохвилинні підходи високо-і низькоінтенсивних аеробних вправ, що чергуються, протягом 30 хвилин за сеанс три дні на тиждень протягом 10 тижнів -значно покращують кардіореспіраторну витривалість у хворих на РА в середньому на 19%.…”