Lipid accumulation and mitochondrial abnormalities are associated with fiber atrophy in skeletal muscle of rats with collagen-induced arthritis

G. Vial (1) , Cécile Coudy-Gandilhon (2) , Alexandre Pinel (2) , Fabien Wauquier (2) , C. Chevenet (3) , Daniel Béchet (2) , Y. Wittrant (2) , Véronique Coxam (2) , Martin Soubrier (1, 2) , Anne Tournadre (1, 2) , Frédéric Capel (2)

1 Service de rhumatologie
2 UNH - Unité de Nutrition Humaine
3 Laboratoire d'Anatomie et de Cytologie Pathologique

Rheumatoid arthritis (RA) has a negative impact on muscle mass, and reduces patient's mobility and autonomy. Furthermore, RA is associated with metabolic comorbidities, notably in lipid homeostasis by unknown mechanisms. To understand the links between the loss in muscle mass and the metabolic abnormalities, arthritis was induced in male Sprague Dawley rats (n=11) using the collagen-induced arthritis model. Rats immunized with bovine type II collagen were compared to a control group of animals (n=11) injected with acetic acid and complete Freund's adjuvant. The clinical severity of the ensuing arthritis was evaluated weekly by a semi-quantitative score. Skeletal muscles from the hind limb were used for the histological analysis and exploration of mitochondrial activity, lipid accumulation, metabolism and regenerative capacities A significant atrophy in tibialis anterior muscle fibers was observed in rats with arthritis despite a non-significant decrease in the weight of the muscles. Despite moderate inflammation, accumulation of triglycerides (P<0.05), reduced mitochondrial DNA copy number (P<0.05) and non-significant dysfunction in mitochondrial cytochrome c oxidase activity were found in the gastrocnemius muscle. Concomitantly, our results suggested an activation of the muscle specific E3 ubiquitin ligases MuRF-1 and MAFbx. Finally, the adipose tissue from the arthritic rats exhibited decreased PPARgamma mRNA suggesting reduced adipogenic capacities. In conclusion, the reduced adipose tissue adipogenic capacity and skeletal muscle mitochondrial capacity are probably involved in the activation of protein catabolism, inhibition of myogenesis, accumulation of lipids and fiber atrophy in skeletal muscle during RA.

Mots clés: Arthritis; Lipids; Mitochondria; Muscle; Sarcopenia

Domaines: Alimentation et Nutrition

G. Vial, Cécile Coudy-Gandilhon, Alexandre Pinel, Fabien Wauquier, C. Chevenet, et al.. Lipid accumulation and mitochondrial abnormalities are associated with fiber atrophy in skeletal muscle of rats with collagen-induced arthritis. Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, 2020, 1865 (2), ⟨10.1016/j.bbalip.2019.158574⟩. ⟨hal-02394660⟩