# Health-enhancing physical activity induce beneficial skeletal muscle mitochondrial adaptations in individuals with rheumatoid arthritis

## TL;DR

Health-enhancing physical activity improves mitochondrial function in skeletal muscle of people with rheumatoid arthritis, but these benefits fade without continued exercise.

## Contribution

This study shows for the first time that HEPA leads to mitochondrial adaptations in skeletal muscle of RA patients.

## Key findings

- Mitochondrial proteins like COX8A and citrate synthase increased after one year of HEPA.
- Compliance with HEPA dropped in the second year, leading to a regression of muscle adaptations.
- Sustained exercise and support are needed to maintain muscle benefits in RA patients.

## Abstract

Rheumatoid arthritis (RA) is a common chronic systemic inflammatory disease that causes musculoskeletal impairments and fatigue. Physical activity is recommended for individuals with RA, and health-enhancing physical activity (HEPA) has been shown to improve health perception and physical fitness in this group. However, the molecular adaptations of skeletal muscle in response to an exercise intervention are still unexplored in individuals with RA. This study aimed to assess the skeletal muscle response to a 2-year HEPA intervention in individuals with RA.

Thirteen individuals with RA (65 ± 2 years old, 13 ± 2 years disease duration) participated. The 2-year HEPA intervention involved 150 min of weekly moderately intense aerobic activity and twice-weekly circuit training. Practical and theoretical physiotherapist support was available the first year, but not the second year. Skeletal muscle biopsies, functional assessments, and mass spectrometry-based proteomics analysis were conducted.

Compliance was high the first year but dropped significantly the second year. Functional improvements in strength, endurance, and lower extremity muscle function (TST) were observed after year 1. Proteomics analysis revealed significant enrichment of mitochondrial proteins including COX8A, citrate synthase, M2OM, NDUFA6, NDUFS2, and VDAC3 after year 1, indicating positive muscle adaptations. However, these changes regressed to baseline levels by year 2.

HEPA can induce beneficial mitochondrial adaptations in skeletal muscle of individuals with RA. However, insufficient compliance and progression in HEPA exercise load led to a reversal of these adaptations. Continuous support and motivation are crucial for maintaining and progressing exercise levels and muscle health in individuals with RA.
Key points• Health-enhancing physical activity (HEPA) can induce beneficial mitochondrial adaptations in the skeletal muscle proteome of individuals with RA.• Positive effects on mitochondrial protein levels aligned with the participants compliance to the HEPA intervention.• Results emphasizes that sustaining and progressing exercise regimen is crucial to maintain beneficial adaptations for individuals with RA.

Key points

• Health-enhancing physical activity (HEPA) can induce beneficial mitochondrial adaptations in the skeletal muscle proteome of individuals with RA.

• Positive effects on mitochondrial protein levels aligned with the participants compliance to the HEPA intervention.

• Results emphasizes that sustaining and progressing exercise regimen is crucial to maintain beneficial adaptations for individuals with RA.

The online version contains supplementary material available at 10.1007/s10067-025-07734-z.