Moellering 2023 Arthritis Res Ther
|Moellering DR, Smith-Johnston K, Kelley C, Sammy MJ, Benedict J, Brock G, Johnson J, Baskin KK, Jarjour WN, Belury MA, Reiser PJ, Nagareddy PR, Hanaoka BY (2023) Association between skeletal muscle mitochondrial dysfunction and insulin resistance in patients with rheumatoid arthritis: a case-control study. https://doi.org/10.1186/s13075-023-03065-z|
» Arthritis Res Ther 25:85. PMID: 37210569 Open Access
Moellering Douglas R, Smith-Johnston Kelley, Kelley Christian, Sammy Melissa J, Benedict Jason, Brock Guy, Johnson Jillian, Baskin Kedryn K, Jarjour Wael N, Belury Martha A, Reiser Peter J, Nagareddy Prabhakara R, Hanaoka Beatriz Y (2023) Arthritis Res Ther
Abstract: Insulin 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.
This 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.
RA 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).
Mitochondrial 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. • Keywords: Mitochondria, Rheumatoid arthritis, Skeletal muscle • Bioblast editor: Plangger M • O2k-Network Lab: US AL Birmingham Moellering DR
Labels: MiParea: Respiration, Patients Pathology: Other
Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, CIV, ROX HRR: Oxygraph-2k