{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:54:25Z","timestamp":1794009265462,"version":"4.8.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03-AG067949"],"award-info":[{"award-number":["R03-AG067949"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-DK089312"],"award-info":[{"award-number":["R01-DK089312"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21-AR076663"],"award-info":[{"award-number":["R21-AR076663"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000654","name":"Marie Curie","doi-asserted-by":"publisher","award":["PIOF-GA-2013-629981"],"award-info":[{"award-number":["PIOF-GA-2013-629981"]}],"id":[{"id":"10.13039\/501100000654","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 <jats:italic>vastus lateralis<\/jats:italic> biopsies were obtained before and after 10\u00a0weeks of HIIT. Following HIIT, improvements in RA cardiorespiratory fitness were associated with changes in RA CD4\u2009+\u2009T cell basal and maximal respiration and skeletal muscle carnitine acetyltransferase (CrAT) enzyme activity. Further, changes in CD4\u2009+\u2009T cell respiration were associated with changes in na\u00efve CD4\u2009+\u2009CCR7\u2009+\u2009CD45RA\u2009+\u2009T 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.<\/jats:p><jats:p>Trial registration: ClinicalTrials.gov, NCT02528344. Registered on 19 August 2015.<\/jats:p>","DOI":"10.1038\/s41598-022-11458-4","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T12:19:05Z","timestamp":1651839545000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness"],"prefix":"10.1038","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct02528344","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Brian J.","family":"Andonian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec","family":"Koss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Koves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R.","family":"Hauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica J.","family":"Hubal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Pober","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet M.","family":"Lord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancie J.","family":"MacIver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. William","family":"St Clair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah M.","family":"Muoio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Kraus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Bartlett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim M.","family":"Huffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"issue":"9746","key":"11458_CR1","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/S0140-6736(10)60826-4","volume":"376","author":"DL Scott","year":"2010","unstructured":"Scott, D. L., Wolfe, F. & Huizinga, T. W. Rheumatoid arthritis. Lancet 376(9746), 1094\u20131108. https:\/\/doi.org\/10.1016\/S0140-6736(10)60826-4 (2010) (Epub 2010\/09\/28).","journal-title":"Lancet"},{"issue":"2","key":"11458_CR2","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1002\/art.20853","volume":"52","author":"H Maradit-Kremers","year":"2005","unstructured":"Maradit-Kremers, H. et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: A population-based cohort study. Arthritis Rheum. 52(2), 402\u2013411. https:\/\/doi.org\/10.1002\/art.20853 (2005) (Epub 2005\/02\/05).","journal-title":"Arthritis Rheum."},{"issue":"12","key":"11458_CR3","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.3899\/jrheum.150166","volume":"42","author":"FA Pinheiro","year":"2015","unstructured":"Pinheiro, F. A., Souza, D. C. & Sato, E. I. A study of multiple causes of death in rheumatoid arthritis. J Rheumatol. 42(12), 2221\u20132228. https:\/\/doi.org\/10.3899\/jrheum.150166 (2015) (Epub 2015\/10\/17).","journal-title":"J Rheumatol."},{"issue":"6","key":"11458_CR4","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1002\/acr.22752","volume":"68","author":"JA Sparks","year":"2016","unstructured":"Sparks, J. A. et al. Rheumatoid arthritis and mortality among women during 36 years of prospective follow-up: Results from the nurses\u2019 health study. Arthritis Care Res. 68(6), 753\u2013762. https:\/\/doi.org\/10.1002\/acr.22752 (2016) (Epub 2015\/10\/17).","journal-title":"Arthritis Care Res."},{"issue":"1","key":"11458_CR5","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/art.23255","volume":"59","author":"T Sokka","year":"2008","unstructured":"Sokka, T. et al. Physical inactivity in patients with rheumatoid arthritis: Data from twenty-one countries in a cross-sectional, international study. Arthritis Rheum. 59(1), 42\u201350. https:\/\/doi.org\/10.1002\/art.23255 (2008) (Epub 2008\/01\/01).","journal-title":"Arthritis Rheum."},{"issue":"1","key":"11458_CR6","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1136\/ard.2004.034769","volume":"65","author":"A Hakkinen","year":"2006","unstructured":"Hakkinen, A. et al. Muscle strength, pain, and disease activity explain individual subdimensions of the Health Assessment Questionnaire disability index, especially in women with rheumatoid arthritis. Ann Rheum Dis. 65(1), 30\u201334. https:\/\/doi.org\/10.1136\/ard.2004.034769 (2006) (Epub 2005\/05\/20).","journal-title":"Ann Rheum Dis."},{"issue":"2","key":"11458_CR7","doi-asserted-by":"publisher","first-page":"106","DOI":"10.3109\/03009742.2014.931456","volume":"44","author":"KM Huffman","year":"2015","unstructured":"Huffman, K. M., Pieper, C. F., Hall, K. S., St Clair, E. W. & Kraus, W. E. Self-efficacy for exercise, more than disease-related factors, is associated with objectively assessed exercise time and sedentary behaviour in rheumatoid arthritis. Scand. J. Rheumatol. 44(2), 106\u2013110. https:\/\/doi.org\/10.3109\/03009742.2014.931456 (2015) (Epub 2014\/09\/16).","journal-title":"Scand. J. Rheumatol."},{"issue":"6","key":"11458_CR8","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1002\/art.23719","volume":"59","author":"JT Giles","year":"2008","unstructured":"Giles, J. T. et al. Abnormal body composition phenotypes in older rheumatoid arthritis patients: Association with disease characteristics and pharmacotherapies. Arthritis Rheum. 59(6), 807\u2013815. https:\/\/doi.org\/10.1002\/art.23719 (2008) (Epub 2008\/06\/03).","journal-title":"Arthritis Rheum."},{"issue":"1","key":"11458_CR9","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13075-016-1215-7","volume":"19","author":"KM Huffman","year":"2017","unstructured":"Huffman, K. M. et al. Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability. Arthritis Res. Ther. 19(1), 12. https:\/\/doi.org\/10.1186\/s13075-016-1215-7 (2017) (Epub 2017\/01\/25).","journal-title":"Arthritis Res. Ther."},{"key":"11458_CR10","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.exger.2017.10.027","volume":"105","author":"Y Li","year":"2018","unstructured":"Li, Y., Goronzy, J. J. & Weyand, C. M. DNA damage, metabolism and aging in pro-inflammatory T cells: Rheumatoid arthritis as a model system. Exp. Gerontol. 105, 118\u2013127. https:\/\/doi.org\/10.1016\/j.exger.2017.10.027 (2018) (Epub 2017\/11\/05).","journal-title":"Exp. Gerontol."},{"issue":"10","key":"11458_CR11","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1084\/jem.20130252","volume":"210","author":"Z Yang","year":"2013","unstructured":"Yang, Z., Fujii, H., Mohan, S. V., Goronzy, J. J. & Weyand, C. M. Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells. J. Exp. Med. 210(10), 2119\u20132134. https:\/\/doi.org\/10.1084\/jem.20130252 (2013) (Epub 2013\/09\/18).","journal-title":"J. Exp. Med."},{"issue":"1","key":"11458_CR12","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1111\/imr.12838","volume":"294","author":"CM Weyand","year":"2020","unstructured":"Weyand, C. M. & Goronzy, J. J. Immunometabolism in the development of rheumatoid arthritis. Immunol. Rev. 294(1), 177\u2013187. https:\/\/doi.org\/10.1111\/imr.12838 (2020) (Epub 2020\/01\/28).","journal-title":"Immunol. Rev."},{"issue":"9","key":"11458_CR13","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1002\/art.40899","volume":"71","author":"X Liu","year":"2019","unstructured":"Liu, X. et al. Long-term physical activity and subsequent risk for rheumatoid arthritis among women: A prospective cohort study. Arthritis Rheumatol. 71(9), 1460\u20131471. https:\/\/doi.org\/10.1002\/art.40899 (2019) (Epub 2019\/03\/29).","journal-title":"Arthritis Rheumatol."},{"issue":"24","key":"11458_CR14","doi-asserted-by":"publisher","first-page":"e653","DOI":"10.1161\/CIR.0000000000000461","volume":"134","author":"R Ross","year":"2016","unstructured":"Ross, R. et al. Importance of assessing cardiorespiratory fitness in clinical practice: A case for fitness as a clinical vital sign: a scientific statement from the american heart association. Circulation 134(24), e653\u2013e699. https:\/\/doi.org\/10.1161\/CIR.0000000000000461 (2016) (Epub 2016\/11\/25).","journal-title":"Circulation"},{"issue":"2","key":"11458_CR15","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/nrrheum.2014.193","volume":"11","author":"FB Benatti","year":"2015","unstructured":"Benatti, F. B. & Pedersen, B. K. Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation. Nat. Rev. Rheumatol. 11(2), 86\u201397. https:\/\/doi.org\/10.1038\/nrrheum.2014.193 (2015) (Epub 2014\/11\/26).","journal-title":"Nat. Rev. Rheumatol."},{"issue":"1","key":"11458_CR16","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/s13075-018-1624-x","volume":"20","author":"DB Bartlett","year":"2018","unstructured":"Bartlett, D. B. et al. Ten weeks of high-intensity interval walk training is associated with reduced disease activity and improved innate immune function in older adults with rheumatoid arthritis: A pilot study. Arthritis Res. Ther. 20(1), 127. https:\/\/doi.org\/10.1186\/s13075-018-1624-x (2018) (Epub 2018\/06\/15).","journal-title":"Arthritis Res. Ther."},{"issue":"1","key":"11458_CR17","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1186\/s13075-018-1786-6","volume":"20","author":"BJ Andonian","year":"2018","unstructured":"Andonian, B. J. et al. Effect of high-intensity interval training on muscle remodeling in rheumatoid arthritis compared to prediabetes. Arthritis Res. Ther. 20(1), 283. https:\/\/doi.org\/10.1186\/s13075-018-1786-6 (2018) (Epub 2018\/12\/28).","journal-title":"Arthritis Res. Ther."},{"issue":"1","key":"11458_CR18","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/s13075-021-02570-3","volume":"23","author":"BJ Andonian","year":"2021","unstructured":"Andonian, B. J. et al. Altered skeletal muscle metabolic pathways, age, systemic inflammation, and low cardiorespiratory fitness associate with improvements in disease activity following high-intensity interval training in persons with rheumatoid arthritis. Arthritis Res. Ther. 23(1), 187. https:\/\/doi.org\/10.1186\/s13075-021-02570-3 (2021) (Epub 2021\/07\/12).","journal-title":"Arthritis Res. Ther."},{"key":"11458_CR19","doi-asserted-by":"publisher","first-page":"8950384","DOI":"10.1155\/2016\/8950384","volume":"2016","author":"C Busquets-Cortes","year":"2016","unstructured":"Busquets-Cortes, C. et al. Training enhances immune cells mitochondrial biosynthesis, fission, fusion, and their antioxidant capabilities synergistically with dietary docosahexaenoic supplementation. Oxid. Med. Cell Longev. 2016, 8950384. https:\/\/doi.org\/10.1155\/2016\/8950384 (2016) (Epub 2016\/10\/05).","journal-title":"Oxid. Med. Cell Longev."},{"issue":"10","key":"11458_CR20","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.3390\/nu10101555","volume":"10","author":"C Busquets-Cortes","year":"2018","unstructured":"Busquets-Cortes, C. et al. Peripheral blood mononuclear cells antioxidant adaptations to regular physical activity in elderly people. Nutrients 10(10), 1555. https:\/\/doi.org\/10.3390\/nu10101555 (2018) (Epub 2018\/10\/24).","journal-title":"Nutrients"},{"issue":"3","key":"11458_CR21","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1152\/japplphysiol.00860.2011","volume":"112","author":"PM Gordon","year":"2012","unstructured":"Gordon, P. M. et al. Resistance exercise training influences skeletal muscle immune activation: A microarray analysis. J. Appl. Physiol. (1985) 112(3), 443\u2013453. https:\/\/doi.org\/10.1152\/japplphysiol.00860.2011 (2012) (Epub 2011\/11\/05).","journal-title":"J. Appl. Physiol. (1985)"},{"issue":"1","key":"11458_CR22","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s12864-016-3388-5","volume":"18","author":"D Liu","year":"2017","unstructured":"Liu, D. et al. Immune adaptation to chronic intense exercise training: New microarray evidence. BMC Genomics 18(1), 29. https:\/\/doi.org\/10.1186\/s12864-016-3388-5 (2017) (Epub 2017\/01\/07).","journal-title":"BMC Genomics"},{"key":"11458_CR23","doi-asserted-by":"publisher","first-page":"35170","DOI":"10.1038\/srep35170","volume":"6","author":"HH Tsai","year":"2016","unstructured":"Tsai, H. H. et al. Exercise training alleviates hypoxia-induced mitochondrial dysfunction in the lymphocytes of sedentary males. Sci. Rep. 6, 35170. https:\/\/doi.org\/10.1038\/srep35170 (2016) (Epub 2016\/10\/13).","journal-title":"Sci. Rep."},{"issue":"1","key":"11458_CR24","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41590-020-00816-x","volume":"22","author":"CM Weyand","year":"2021","unstructured":"Weyand, C. M. & Goronzy, J. J. The immunology of rheumatoid arthritis. Nat. Immunol. 22(1), 10\u201318. https:\/\/doi.org\/10.1038\/s41590-020-00816-x (2021) (Epub 2020\/12\/02).","journal-title":"Nat. Immunol."},{"issue":"11","key":"11458_CR25","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1111\/sms.13506","volume":"29","author":"GP Dorneles","year":"2019","unstructured":"Dorneles, G. P. et al. Cardiorespiratory fitness modulates the proportions of monocytes and T helper subsets in lean and obese men. Scand. J. Med. Sci. Sports 29(11), 1755\u20131765. https:\/\/doi.org\/10.1111\/sms.13506 (2019) (Epub 2019\/06\/27).","journal-title":"Scand. J. Med. Sci. Sports"},{"issue":"1","key":"11458_CR26","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1007\/s11357-016-9879-0","volume":"38","author":"LC Silva","year":"2016","unstructured":"Silva, L. C. et al. Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations. Age 38(1), 24. https:\/\/doi.org\/10.1007\/s11357-016-9879-0 (2016) (Epub 2016\/02\/13).","journal-title":"Age"},{"issue":"8","key":"11458_CR27","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1016\/j.bbi.2011.07.226","volume":"25","author":"G Spielmann","year":"2011","unstructured":"Spielmann, G. et al. Aerobic fitness is associated with lower proportions of senescent blood T-cells in man. Brain Behav. Immun. 25(8), 1521\u20131529. https:\/\/doi.org\/10.1016\/j.bbi.2011.07.226 (2011) (Epub 2011\/07\/26).","journal-title":"Brain Behav. Immun."},{"key":"11458_CR28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.604591","volume":"11","author":"IJ Rodriguez","year":"2020","unstructured":"Rodriguez, I. J. et al. Immunosenescence study of T cells: A systematic review. Front. Immunol. 11, 604591. https:\/\/doi.org\/10.3389\/fimmu.2020.604591 (2020) (Epub 2021\/02\/02).","journal-title":"Front. Immunol."},{"key":"11458_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103409","volume":"68","author":"J Zhang","year":"2021","unstructured":"Zhang, J., He, T., Xue, L. & Guo, H. Senescent T cells: A potential biomarker and target for cancer therapy. EBioMedicine 68, 103409. https:\/\/doi.org\/10.1016\/j.ebiom.2021.103409 (2021) (Epub 2021\/05\/29).","journal-title":"EBioMedicine"},{"key":"11458_CR30","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1146\/annurev-physiol-020518-114310","volume":"81","author":"DA Hood","year":"2019","unstructured":"Hood, D. A., Memme, J. M., Oliveira, A. N. & Triolo, M. Maintenance of skeletal muscle mitochondria in health, exercise, and aging. Annu. Rev. Physiol. 81, 19\u201341. https:\/\/doi.org\/10.1146\/annurev-physiol-020518-114310 (2019) (Epub 2018\/09\/15).","journal-title":"Annu. Rev. Physiol."},{"issue":"1","key":"11458_CR31","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.cmet.2015.06.003","volume":"22","author":"SE Seiler","year":"2015","unstructured":"Seiler, S. E. et al. Carnitine acetyltransferase mitigates metabolic inertia and muscle fatigue during exercise. Cell Metab. 22(1), 65\u201376. https:\/\/doi.org\/10.1016\/j.cmet.2015.06.003 (2015) (Epub 2015\/07\/15).","journal-title":"Cell Metab."},{"issue":"11","key":"11458_CR32","doi-asserted-by":"publisher","first-page":"2282","DOI":"10.1007\/s00125-014-3343-4","volume":"57","author":"KM Huffman","year":"2014","unstructured":"Huffman, K. M. et al. Metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness. Diabetologia 57(11), 2282\u20132295. https:\/\/doi.org\/10.1007\/s00125-014-3343-4 (2014) (Epub 2014\/08\/06).","journal-title":"Diabetologia"},{"issue":"1","key":"11458_CR33","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28(1), 27\u201330. https:\/\/doi.org\/10.1093\/nar\/28.1.27 (2000) (Epub 1999\/12\/11).","journal-title":"Nucleic Acids Res."},{"issue":"D1","key":"11458_CR34","doi-asserted-by":"publisher","first-page":"D506","DOI":"10.1093\/nar\/gky1049","volume":"47","author":"C UniProt","year":"2019","unstructured":"UniProt, C. UniProt: A worldwide hub of protein knowledge. Nucleic Acids Res. 47(D1), D506\u2013D515. https:\/\/doi.org\/10.1093\/nar\/gky1049 (2019) (Epub 2018\/11\/06).","journal-title":"Nucleic Acids Res."},{"key":"11458_CR35","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1146\/annurev-immunol-032712-095956","volume":"31","author":"NJ MacIver","year":"2013","unstructured":"MacIver, N. J., Michalek, R. D. & Rathmell, J. C. Metabolic regulation of T lymphocytes. Annu. Rev. Immunol. 31, 259\u2013283. https:\/\/doi.org\/10.1146\/annurev-immunol-032712-095956 (2013) (Epub 2013\/01\/10).","journal-title":"Annu. Rev. Immunol."},{"issue":"2","key":"11458_CR36","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.immuni.2018.01.007","volume":"48","author":"BV Kumar","year":"2018","unstructured":"Kumar, B. V., Connors, T. J. & Farber, D. L. Human T cell development, localization, and function throughout life. Immunity 48(2), 202\u2013213. https:\/\/doi.org\/10.1016\/j.immuni.2018.01.007 (2018) (Epub 2018\/02\/22).","journal-title":"Immunity"},{"issue":"10","key":"11458_CR37","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1007\/s00421-017-3684-z","volume":"117","author":"C Busquets-Cortes","year":"2017","unstructured":"Busquets-Cortes, C. et al. Training and acute exercise modulates mitochondrial dynamics in football players\u2019 blood mononuclear cells. Eur. J. Appl. Physiol. 117(10), 1977\u20131987. https:\/\/doi.org\/10.1007\/s00421-017-3684-z (2017) (Epub 2017\/07\/28).","journal-title":"Eur. J. Appl. Physiol."},{"issue":"2","key":"11458_CR38","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1152\/japplphysiol.00777.2018","volume":"126","author":"CP Hedges","year":"2019","unstructured":"Hedges, C. P. et al. Peripheral blood mononuclear cells do not reflect skeletal muscle mitochondrial function or adaptation to high-intensity interval training in healthy young men. J. Appl. Physiol. (1985) 126(2), 454\u2013461. https:\/\/doi.org\/10.1152\/japplphysiol.00777.2018 (2019) (Epub 2018\/12\/21).","journal-title":"J. Appl. Physiol. (1985)"},{"issue":"4","key":"11458_CR39","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1152\/jappl.2001.91.4.1708","volume":"91","author":"A Steensberg","year":"2001","unstructured":"Steensberg, A. et al. Strenuous exercise decreases the percentage of type 1 T cells in the circulation. J. Appl. Physiol. (1985) 91(4), 1708\u20131712. https:\/\/doi.org\/10.1152\/jappl.2001.91.4.1708 (2001) (Epub 2001\/09\/25).","journal-title":"J. Appl. Physiol. (1985)"},{"issue":"9","key":"11458_CR40","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1089\/jir.2013.0031","volume":"34","author":"MW Kakanis","year":"2014","unstructured":"Kakanis, M. W. et al. T helper cell cytokine profiles after endurance exercise. J. Interferon Cytokine Res. 34(9), 699\u2013706. https:\/\/doi.org\/10.1089\/jir.2013.0031 (2014) (Epub 2014\/03\/29).","journal-title":"J. Interferon Cytokine Res."},{"key":"11458_CR41","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.jaut.2012.07.009","volume":"40","author":"JO Jin","year":"2013","unstructured":"Jin, J. O., Han, X. & Yu, Q. Interleukin-6 induces the generation of IL-10-producing Tr1 cells and suppresses autoimmune tissue inflammation. J. Autoimmun. 40, 28\u201344. https:\/\/doi.org\/10.1016\/j.jaut.2012.07.009 (2013) (Epub 2012\/08\/28).","journal-title":"J. Autoimmun."},{"key":"11458_CR42","doi-asserted-by":"crossref","unstructured":"Lavin. K. M., Perkins, R., Jemiolo, B., Raue, U., Trappe, S. W., Trappe, T. A. Effects of aging and lifelong aerobic exercise on basal and exercise-induced inflammation. J. Appl. Physiol. (1985) (2019).","DOI":"10.1152\/japplphysiol.00495.2019"},{"issue":"5","key":"11458_CR43","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1016\/j.jaci.2015.10.035","volume":"137","author":"M Weinhold","year":"2016","unstructured":"Weinhold, M. et al. Physical exercise modulates the homeostasis of human regulatory T cells. J. Allergy Clin. Immunol. 137(5), 1607-1610.e8. https:\/\/doi.org\/10.1016\/j.jaci.2015.10.035 (2016) (Epub 2016\/01\/18).","journal-title":"J. Allergy Clin. Immunol."},{"issue":"3","key":"11458_CR44","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.jshs.2018.09.009","volume":"8","author":"DC Nieman","year":"2019","unstructured":"Nieman, D. C. & Wentz, L. M. The compelling link between physical activity and the body\u2019s defense system. J. Sport Health Sci. 8(3), 201\u2013217. https:\/\/doi.org\/10.1016\/j.jshs.2018.09.009 (2019) (Epub 2019\/06\/14).","journal-title":"J. Sport Health Sci."},{"issue":"5","key":"11458_CR45","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.cmet.2012.04.010","volume":"15","author":"DM Muoio","year":"2012","unstructured":"Muoio, D. M. & Neufer, P. D. Lipid-induced mitochondrial stress and insulin action in muscle. Cell Metab. 15(5), 595\u2013605. https:\/\/doi.org\/10.1016\/j.cmet.2012.04.010 (2012) (Epub 2012\/05\/09).","journal-title":"Cell Metab."},{"issue":"4","key":"11458_CR46","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1194\/jlr.M043448","volume":"55","author":"SE Seiler","year":"2014","unstructured":"Seiler, S. E. et al. Obesity and lipid stress inhibit carnitine acetyltransferase activity. J. Lipid Res. 55(4), 635\u2013644. https:\/\/doi.org\/10.1194\/jlr.M043448 (2014) (Epub 2014\/01\/08).","journal-title":"J. Lipid Res."},{"issue":"34","key":"11458_CR47","doi-asserted-by":"publisher","first-page":"22840","DOI":"10.1074\/jbc.M109.032888","volume":"284","author":"RC Noland","year":"2009","unstructured":"Noland, R. C. et al. Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control. J. Biol. Chem. 284(34), 22840\u201322852. https:\/\/doi.org\/10.1074\/jbc.M109.032888 (2009) (Epub 2009\/06\/26).","journal-title":"J. Biol. Chem."},{"issue":"5","key":"11458_CR48","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.cmet.2012.04.005","volume":"15","author":"DM Muoio","year":"2012","unstructured":"Muoio, D. M. et al. Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. Cell Metab. 15(5), 764\u2013777. https:\/\/doi.org\/10.1016\/j.cmet.2012.04.005 (2012) (Epub 2012\/05\/09).","journal-title":"Cell Metab."},{"issue":"9","key":"11458_CR49","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1136\/ard.2010.138461","volume":"69","author":"D Aletaha","year":"2010","unstructured":"Aletaha, D. et al. 2010 rheumatoid arthritis classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative. Ann. Rheum. Dis. 69(9), 1580\u20131588. https:\/\/doi.org\/10.1136\/ard.2010.138461 (2010) (Epub 2010\/08\/12).","journal-title":"Ann. Rheum. Dis."},{"issue":"7","key":"11458_CR50","doi-asserted-by":"publisher","first-page":"609","DOI":"10.3109\/00365517509095787","volume":"35","author":"J Bergstrom","year":"1975","unstructured":"Bergstrom, J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand. J. Clin. Lab Invest. 35(7), 609\u2013616 (1975) (Epub 1975\/11\/01).","journal-title":"Scand. J. Clin. Lab Invest."},{"issue":"11","key":"11458_CR51","doi-asserted-by":"publisher","first-page":"4915","DOI":"10.1172\/JCI74830","volume":"124","author":"L Lindeboom","year":"2014","unstructured":"Lindeboom, L. et al. Long-echo time MR spectroscopy for skeletal muscle acetylcarnitine detection. J. Clin. Invest. 124(11), 4915\u20134925. https:\/\/doi.org\/10.1172\/JCI74830 (2014) (Epub 2014\/10\/02).","journal-title":"J. Clin. Invest."},{"issue":"12","key":"11458_CR52","doi-asserted-by":"publisher","first-page":"8106","DOI":"10.1074\/jbc.M113.511535","volume":"289","author":"KL DeBalsi","year":"2014","unstructured":"DeBalsi, K. L. et al. Targeted metabolomics connects thioredoxin-interacting protein (TXNIP) to mitochondrial fuel selection and regulation of specific oxidoreductase enzymes in skeletal muscle. J. Biol. Chem. 289(12), 8106\u20138120. https:\/\/doi.org\/10.1074\/jbc.M113.511535 (2014) (Epub 2014\/02\/01).","journal-title":"J. Biol. Chem."},{"issue":"2","key":"11458_CR53","first-page":"84","volume":"6","author":"AAN Vigels\u00f8","year":"2014","unstructured":"Vigels\u00f8, A. A. N. & Dela, F. The relationship between skeletal muscle mitochondrial citrate synthase activity and whole body oxygen uptake adaptations in response to exercise training. Int. J. Physiol. Pathophysiol. Pharmacol. 6(2), 84\u2013101 (2014).","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"issue":"4","key":"11458_CR54","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.cmet.2009.02.002","volume":"9","author":"CB Newgard","year":"2009","unstructured":"Newgard, C. B. et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 9(4), 311\u2013326. https:\/\/doi.org\/10.1016\/j.cmet.2009.02.002 (2009) (Epub 2009\/04\/10).","journal-title":"Cell Metab."},{"issue":"6","key":"11458_CR55","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/j.cct.2005.09.003","volume":"26","author":"AM Haqq","year":"2005","unstructured":"Haqq, A. M. et al. The Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project: Rationale and design. Contemp. Clin. Trials 26(6), 616\u2013625. https:\/\/doi.org\/10.1016\/j.cct.2005.09.003 (2005) (Epub 2005\/10\/22).","journal-title":"Contemp. Clin. Trials"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-11458-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-11458-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-11458-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T02:51:45Z","timestamp":1669344705000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-11458-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,6]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["11458"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-11458-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,6]]},"assertion":[{"value":"17 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7450"}}