Arthritis Research & Therapy | |
Association between skeletal muscle mitochondrial dysfunction and insulin resistance in patients with rheumatoid arthritis: a case–control study | |
Research | |
Christian Kelley1  Guy Brock2  Jason Benedict2  Martha A. Belury3  Kelley Smith-Johnston4  Douglas R. Moellering4  Melissa J. Sammy4  Kedryn K. Baskin5  Prabhakara R. Nagareddy6  Jillian Johnson6  Peter J. Reiser7  Beatriz Y. Hanaoka8  Wael N. Jarjour8  | |
[1] Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, AL, USA;Department of Biomedical Bioinformatics, College of Medicine, The Ohio State University, Columbus, OH, USA;Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, Columbus, OH, USA;Department of Nutrition Sciences, School of Health Professions, University of Alabama at Birmingham, Birmingham, AL, USA;Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, USA;Department of Surgery, College of Medicine, The Ohio State University, Columbus, OH, USA;Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA;Division of Rheumatology and Immunology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA; | |
关键词: Rheumatoid arthritis; Skeletal muscle; Mitochondria; | |
DOI : 10.1186/s13075-023-03065-z | |
received in 2023-04-19, accepted in 2023-05-09, 发布年份 2023 | |
来源: Springer | |
【 摘 要 】
BackgroundInsulin resistance affects a substantial proportion of patients with rheumatoid arthritis (RA). Skeletal muscle mitochondrial dysfunction results in the accumulation of lipid intermediates that interfere with insulin signaling. We therefore sought to determine if lower oxidative phosphorylation and muscle mitochondrial content are associated with insulin resistance in patients with RA.MethodsThis was a cross-sectional prospective study of RA patients. Matsuda index from the glucose tolerance test was used to estimate insulin sensitivity. Mitochondrial content was measured by citrate synthase (CS) activity in snap-frozen muscle samples. Mitochondrial function was measured by using high-resolution respirometry of permeabilized muscle fibers and electron transport chain complex IV enzyme kinetics in isolated mitochondrial subpopulations.ResultsRA participants demonstrated lower insulin sensitivity as measured by the Matsuda index compared to controls [median 3.95 IQR (2.33, 5.64) vs. 7.17 (5.83, 7.75), p = 0.02]. There was lower muscle mitochondrial content among RA vs. controls [median 60 mU/mg IQR (45, 80) vs. 79 mU/mg (65, 97), p = 0.03]. Notably, OxPhos normalized to mitochondrial content was higher among RA vs. controls [mean difference (95% CI) = 0.14 (0.02, 0.26), p = 0.03], indicating a possible compensatory mechanism for lower mitochondrial content or lipid overload. Among RA participants, the activity of muscle CS activity was not correlated with the Matsuda index (ρ = − 0.05, p = 0.84), but it was positively correlated with self-reported (IPAQ) total MET-minutes/week (ρ = 0.44, p = 0.03) and Actigraph-measured time on physical activity (MET rate) (ρ = 0.47, p = 0.03).ConclusionsMitochondrial content and function were not associated with insulin sensitivity among participants with RA. However, our study demonstrates a significant association between muscle mitochondrial content and physical activity level, highlighting the potential for future exercise interventions that enhance mitochondrial efficiency in RA patients.
【 授权许可】
CC BY
© The Author(s) 2023
【 预 览 】
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