Abstract
Background: Patients with multiple sclerosis (MS) experience reduced exercise tolerance that substantially reduces quality of life. The mechanisms underpinning exercise intolerance in MS are not fully clear. This study aimed to determine the contributions of the cardiopulmonary system and peripheral muscle in MS-induced exercise intolerance before and after exercise training. Methods: Twenty-three patients with MS (13 women) and 20 age-matched and sex-matched healthy controls (13 women) performed a cardiopulmonary exercise test. Muscle fibre type composition, size, succinate dehydrogenase (SDH) activity, capillarity, and gene expression and proteins related to mitochondrial density were determined in vastus lateralis muscle biopsies. Nine MS patients (five women) were re-examined following a 12 week exercise training programme consisting of high-intensity cycling interval and resistance training. Results: Patients with MS had lower maximal oxygen uptake compared with healthy controls (V̇O2peak, 25.0 ± 8.5 vs. 35.7 ± 6.4 mL/kg/min, P < 0.001). The lower gas exchange threshold (MS: 14.5 ± 5.5 vs. controls: 19.7 ± 2.9 mL/kg/min, P = 0.01) and slope of V̇O2 versus work rate (MS: 9.5 ± 1.7 vs. controls: 10.8 ± 1.1 mL/min/W, P = 0.01) suggested an intramuscular contribution to exercise intolerance in patients with MS. Muscle SDH activity was 22% lower in MS (P = 0.004), and strongly correlated with several indices of whole-body exercise capacity in MS patients (e.g. V̇O2peak, Spearman's ρ = 0.81, P = 0.002), but not healthy controls (ρ = 0.24, P = 0.38). In addition, protein levels of mitochondrial OXPHOS complexes I (−40%, P = 0.047) and II (−45%, P = 0.026) were lower in MS patients versus controls. Muscle capillary/fibre ratio correlated with V̇O2peak in healthy controls (ρ = 0.86, P < 0.001) but not in MS (ρ = 0.35, P = 0.22), and did not differ between groups (1.41 ± 0.30 vs. 1.47 ± 0.38, P = 0.65). Expression of genes involved in mitochondrial function, such as PPARA, PPARG, and TFAM, was markedly reduced in muscle tissue samples of MS patients (all P < 0.05). No differences in muscle fibre type composition or size were observed between groups (all P > 0.05). V̇O2peak increased by 23% following exercise training in MS (P < 0.001); however, no changes in muscle capillarity, SDH activity, gene or protein expression were observed (all P > 0.05). Conclusions: Skeletal muscle oxidative phenotype (mitochondrial complex I and II content, SDH activity) is lower in patients with MS, contributing to reduced exercise tolerance. However, skeletal muscle mitochondria appeared resistant to the beneficial effects of exercise training, suggesting that other physiological systems, at least in part, drive the improvements in exercise capacity following exercise training in MS.
Original language | English |
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Pages (from-to) | 2537-2550 |
Number of pages | 14 |
Journal | Journal of Cachexia, Sarcopenia and Muscle |
Volume | 13 |
Issue number | 5 |
Early online date | 4 Aug 2022 |
DOIs | |
Publication status | Published - Oct 2022 |
Bibliographical note
Funding Information:We are grateful to MS-Liga Vlaanderen (Belgium) for financial support and to Wendy Noort (Vrije Universiteit Amsterdam, The Netherlands) for her advice and assistance for the histochemistry analyses. Figures were created using GraphPad Prism v7.04. The authors of this manuscript certify that they comply with the ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle.
Funding Information:
We are grateful to MS‐Liga Vlaanderen (Belgium) for financial support and to Wendy Noort (Vrije Universiteit Amsterdam, The Netherlands) for her advice and assistance for the histochemistry analyses. Figures were created using GraphPad Prism v7.04. The authors of this manuscript certify that they comply with the ethical guidelines for authorship and publishing in the . Journal of Cachexia, Sarcopenia and Muscle
Publisher Copyright:
© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.
Keywords
- Exercise capacity
- Exercise therapy
- Mitochondria
- Multiple sclerosis
- Oxidative metabolism
- Skeletal muscle