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.
Highlights
Muscle atrophy is the loss of muscle mass resulting from a reduction in muscle fiber area or density due to a decrease in protein synthesis and an increase in muscle protein breakdown; these processes activate two major systems: the proteasomal and the autophagic-lysosomal system [1,2,3]
This study evaluated the effects of n-3 Polyunsaturated fatty acids (PUFAs) on the development of dexamethasone-induced muscle atrophy through histological analysis, expression of genes involved in protein synthesis and degradation, and assessment of expression of proteins involved in the IGF-1/PI3k/Akt/mTOR pathway
Some studies have shown that EPA and n-3 PUFA supplementation can alleviate muscle atrophy related to cancer, fasting, and septicemia [36,37,38]
Summary
Muscle atrophy is the loss of muscle mass resulting from a reduction in muscle fiber area or density due to a decrease in protein synthesis and an increase in muscle protein breakdown; these processes activate two major systems: the proteasomal (ubiquitin-proteasome system or UPS) and the autophagic-lysosomal system [1,2,3]. Many studies have shown that glucocorticoids cause muscle atrophy through the IGF-1/PI-3K/Akt/mTOR and myostatin/Smad2/3 pathways [7, 8], and through the regulation of muscle transcription factors, atrogenes, and cathepsins [8, 9] Some of these mechanisms involve the reduction in mTOR activity induced by an increase of REDD1 (regulated in development and DNA damage responses 1) [10], and an increase in the GSK3β protein. This study evaluated the effects of n-3 PUFA (capsule formulation) on the development of dexamethasone-induced muscle atrophy through histological analysis, expression of genes involved in protein synthesis and degradation, and assessment of expression of proteins involved in the IGF-1/PI3k/Akt/mTOR pathway
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