Eicosapentaenoic acid attenuates arthritis-induced muscle wasting acting on atrogin-1 and on myogenic regulatory factors

Abstract

Castillero E, Martín AI, López-Menduiña M, Villanúa MA, López-Calderón A. Eicosapentaenoic acid attenuates arthritis-induced muscle wasting acting on atrogin-1 and on myogenic regulatory factors. Am J Physiol Regul Integr Comp Physiol 297: R1322-R1331, 2009. First published September 9, 2009 doi:10.1152/ajpregu.00388.2009.-Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that has anti-inflammatory and anticachectic actions. The aim of this work was to elucidate whether EPA administration is able to prevent an arthritis-induced decrease in body weight and muscle wasting in rats. Arthritis was induced by intradermal injection of Freund's adjuvant; 3 days later, nine rats received 1 g/kg EPA or coconut oil daily. All rats were killed 15 days after adjuvant injection. EPA administration decreased the external signs of arthritis and paw volume as well as liver TNF-␣ mRNA. EPA did not modify arthritis-induced decrease in food intake or body weight gain. However, EPA treatment prevented arthritis-induced increase in muscle TNF-␣ and atrogin-1, whereas it attenuated the decrease in gastrocnemius weight and the increase in MuRF1 mRNA. Arthritis not only decreased myogenic regulatory factors but also increased PCNA, MyoD, and myogenin mRNA in the gastrocnemius. Western blot analysis showed that changes in protein content followed the pattern seen with mRNA. In the control rats, EPA administration increased PCNA and MyoD mRNA and protein.In arthritic rats, EPA did not modify the stimulatory effect of arthritis on these myogenic regulatory factors. The results suggest that in experimental arthritis, in addition to its anti-inflammatory effect, EPA treatment attenuates muscle wasting by decreasing atrogin-1 and MuRF1 gene expression and increasing the transcription factors that regulate myogenesis. adjuvant-induced arthritis; ubiquitin-proteasome system; MyoD; myogenin; proliferating cell nuclear antigen CHRONIC INFLAMMATORY DISEASES such as cancer, sepsis, and rheumatoid arthritis are associated with a decrease in body weight, skeletal muscle atrophy, and cachexia. Cachexia is a complex metabolic syndrome associated with underlying

Fenofibrate, a PPARα agonist, decreases atrogenes and myostatin expression and improves arthritis-induced skeletal muscle atrophy

“…The fact that fenofibrate prevented an arthritis-induced increase in these myogenic regulatory factors can be due to its anti-inflammatory effect. As mentioned above, EPA, a natural ligand of PPARs, prevents arthritis-induced increases in atrogin-1 and MuRF1 (11). However, PCNA, MyoD, and myogenin expression remained elevated in arthritic rats treated with EPA.…”

“…Several clinical studies have shown benefits from fish oil and EPA in patients with rheumatoid arthritis (26,50). In arthritic rats, we have reported that EPA administration decreases not only the external signs of inflammation but also arthritisinduced muscle proteolysis (11). Therefore, it is possible that the anticachetic effect of EPA is mediated through PPAR activation.…”

Comparison of the effects of the n-3 polyunsaturated fatty acid eicosapentaenoic and fenofibrate on the inhibitory effect of arthritis on IGF1

“…EPA administration prevented the inhibitory effect of arthritis on IGF1 and on its expression in the liver, without increasing body weight gain. The absence of effect of EPA on body weight gain can be due to the fact that EPA does not modify food intake in arthritic rats (Volker et al 2000, Castillero et al 2009b. A lack of effect of EPA on body weight together with a protective effect on muscle has also been reported in dystrophic muscle degeneration (Machado et al 2011).…”

“…It is well known that EPA has an anti-inflammatory effect decreasing proinflammatory cytokines (Tashiro et al 1998, Zhao et al 2004) and both cyclooxygenase-2 activity and expression (Hurst et al 2009). Furthermore, EPA is able to decrease joint inflammation in rheumatoid arthritis patients (James & Cleland 1997, Simopoulos 2002) and in arthritic rats (Leslie et al 1985, Volker et al 2000, Castillero et al 2009b. In addition to its anti-inflammatory effect, EPA ameliorates arthritis-induced skeletal muscle wasting by decreasing atrogin-1 and Murf-1 gene expression and also increasing the transcription factors that regulate myogenesis (Castillero et al 2009a).…”

Combined approach to counteract experimental cancer cachexia: eicosapentenoic acid and training exercise

“…Summarizing, EPA does not appear suitable to prevent cancer cachexia, despite being a good candidate for the treatment of other experimental wasting conditions such as diabetes [37] and arthritis [38]. The different effectiveness of EPA in counteracting the various types of muscle atrophies may depend on the underlying pathogenetic mechanisms.…”