Adjuvant-induced arthritis is an animal model of cachexia accompanied by skeletal muscle atrophy and body weight loss. Muscle wasting is associated with the upregulation of proteolysis by ubiquitin-protheasome pathway. Peroxisomal proliferator-activated receptor alpha (PPARa) is reported to play a major role regulating inflammatory processes.

Aim: 

To evaluate whether PPARa agonist fenofibrate is able to prevent the sympthoms of arthritis and its effects on gastrocnemius muscle.

Methods: 

Arthritis was induced in male Wistar rats by an intradermal injection of Freund's adjuvant. Three days after the injection, control and arthritis rats were divided in two experimental groups. One group was daily gavaged with 300mg/kg of fenofibrate and the other was gavaged with vehicle. After 12 days of treatment rats were killed by decapitation, and gastrocnemius muscles were weighted and dissected. Gene expression of ubiquitin ligases atrogin-1 and Murf-1, and myostatin in gastrocnemius muscle were measured by real-time PCR.

Results: 

Fenofibrate administration ameliorated arthritis score and hindpaw swelling in arthritic rats (P<0.01). Arthritis decreased body weight gain and the weight of skeletal muscle (P<0.01), whereas fenofibrate reduced skeletal muscle weight loss (P<0.05). Fenofibrate prevented arthritis-induced increase in atrogin-1 and Murf-1 mRNA in gastrocnemius muscle (P<0.01). Negative regulator of muscle growth myostatin was not modified by arthritis; however fenofibrate decreased its expression in gastrocnemius muscle (P<0.01).

Conclusion: 

Fenofibrate attenuates external sympthoms of arthritis and muscle proteolysis downregulating the expression of atrogin-1, MuRF-1 and myostatin.

This work was supported by IV Convocatoria de ayudas a la investigación de la Fundación Mutua Madrileña, a grant to Castillero E. (Gobierno Vasco, BFI06.31), and a grant to López-Menduiña M(BFU, 2006-11899).