The Effects of Omega-3 Fatty Acid Supplementation on Dexamethasone-Induced Muscle Atrophy

Abstract

Corticosteroids cause muscle atrophy by acting on proteasomal and lysosomal systems and by affecting pathways related to muscular trophysm, such as the IGF-1/PI-3k/Akt/mTOR. Omega-3 fatty acid (n-3) has been used beneficially to attenuate muscle atrophy linked to sepsis and cachexia; however, its effect on dexamethasone-induced muscle atrophy has not been evaluated. Objectives. We evaluated whether n-3 supplementation could mitigate the development of dexamethasone-induced muscle atrophy. Methods. Two groups of Wistar rats were orally supplemented with n-3 or vehicle solution for 40 days. In the last 10 days, dexamethasone, or saline solution, was administrated establishing four groups: control, dexamethasone, n-3, and dexamethasone + n-3. The cross-sectional areas of muscle fibers, gene expression (MyoD, Myogenin, MuRF-1, and Atrogin-1), and protein expression (Akt, GSK3β, FOXO3a, and mTOR) were assessed. Results. Dexamethasone induced a significant loss in body and muscle weight, atrophy in type 2B fibers, and decreased expression of P-Akt, P-GSK3β, and P-FOXO3a. N-3 supplementation did not attenuate the negative effects of dexamethasone on skeletal muscle; instead, it caused atrophy in type 1, 2A, reduced the expression of Myogenin, and increased the expression of Atrogin-1. Conclusion. Food supplements containing n-3 are usually healthful, but they may potentiate some of the side effects of glucocorticoids.

The role of E3 ubiquitin-ligases MuRF-1 and MAFbx in loss of skeletal muscle mass

“…In accordance, mRNA levels of MuRF-1 and MAFbx were decreased [93]. In contrast with the above studies, omega 3 supplementation to dexamethasone treated rats did not attenuate the negative effects of dexamethasone on skeletal muscle; instead, it caused muscle atrophy, reduced myogenin expression, and increased the expression of MAFbx with no significant effects on Akt and FOXO3a expression [94]. Similarly, in a mouse model of cancer cachexia, treatment with the omega-3 fatty acid eicosapentaenoic acid (EPA) was found to increase MuRF-1 and MAFbx mRNA levels [95].…”

Neuraminidase-1 mediates skeletal muscle regeneration

“…Indeed, atrogin-1 is recognized as the E3 ligase responsible for MyoD degradation [31], what could explain the low levels of MyoD in these mice, even with upregulated gene. Increased expression of atrogin-1 and reduced expression of myogenin had previously been linked to a model of skeletal muscle atrophy [32]. In turn, MuRF-1 controls the half-life of important structural muscle proteins [33–35], including myosin heavy chains [33, 34].…”

Efeitos de diferentes glicocorticoides sobre as vias moleculares de regulação do trofismo muscular em ratos e o efeito do EPA/DHA na atrofia muscular induzida pela dexametasona

“…Em um estudo recentemente realizado por nós, com o objetivo de avaliar o efeito do Ômega-3 no desenvolvimento da atrofia muscular induzida pelo dexametasona (Fappi et al, 2014) os grupos de animais que tiveram associação da dexametasona (5mg/kg/dia) com o Ômega-3 (EPA/DHA), apresentaram níveis de ácido araquidônico (AA) reduzidos em comparação com o grupo CT (42,12%). Demonstramos ainda que a utilização prévia e concomitante de EPA/DHA associada ao dexametasona em ratos, conduziu a um maior prejuízo muscular que em comparação com a dexametasona de forma isolada, com maiores níveis de atrofia musculares em fibras do tipo 1 e 2A associado a uma maior expressão de atrogenes como Atrogina-1 e diminuição na miogênese muscular, com diminuída expressão da Miogenina (MYOG).…”

“…Alguns candidatos para atenuação da atrofia muscular que mostraram efeitos benéficos são a testosterona (Qin et al, 2010;Wu et al, 2010), creatina (Menezes et al, 2007, HMB (metabólito da leucina) (Wyke et al, 2004) entre outros. Entretanto, o uso de ômega-3 (ácido graxo poli-insaturado) associado a dexametasona causou aumento da atrofia muscular em fibras usualmente poupadas e aumento da expressão de Atrogina-1 (Fappi et al, 2014).…”

“…(EPA/DHA), ocasionou maior prejuízo muscular que em comparação com a dexametasona de forma isolada, com maiores níveis de atrofia musculares em fibras do tipo 1 e 2A associado a uma maior expressão de atrogenes como Atrogina-1 e diminuição na miogênese muscular, com diminuída expressão da Miogenina (MYOG) (Fappi et al, 2014 Shulman et al, 1990;Brook et al, 2016).…”