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Effects of omega-3 fatty acid in preventing dexamethasone-induced muscle atrophy

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Author(s):
Alan Fappi
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
Defense date:
Examining board members:
Edmar Zanoteli; Umbertina Conti Reed; Lydia Uraco Yamamoto
Advisor: Edmar Zanoteli
Abstract

Many conditions can be related to muscle atrophy, such as inactivity, aging, sepsis, diabetes, cancer, as well as, glucocorticoid treatment. All these conditions lead to muscle atrophy through mechanisms that include increase of protein degradation and/or decrease of protein synthesis involving at least five systems: lysossomal, calpain, caspases, metaloproteinases and ubiquitin proteasome system (UPS). Glucocorticoids, such as dexamethasone cause muscle atrophy acting in almost all of these systems, with a significant UPS activation and affecting an important pathway related to muscular trophism, IGF-1/PI-3k/Akt/mTOR pathway. Poly-unsaturated fatty acids, such as Omega-3 (omega-3), have been used beneficially to attenuation of muscle atrophy that occur in sepsis and cachexia related to cancer, however, its action in the glucocorticoid-induced muscle atrophy, has never been evaluated. Objective: Assess whether the omega-3 supplementation would influence the development of dexamethasone-induced muscle atrophy in rats. Methods: Twenty four Wistar rats supplemented and non-supplemented with omega-3 (40 days) were submitted to dexamethasone administration (5mg/kg/day) during the last 10 days, thus establishing 4 groups: control (CT), dexamethasone (DX), omega-3 and dexamethasone+omega-3 (DX+ omega-3). The amount of large and small movements in open field; muscle fiber cross sectional areas (I, IIA and IIB); MyoD, Myogenin, MuRF-1, Atrogin-1 and Myostatin gene expression; and protein expression of Akt, GSK3omega, FOXO3a and mTOR, total and phosphorylated forms were assessed, respectively, by: motor behavior testing, histological reactions, Real-time PCR and Western Blotting analysis. Results: Dexamethasone administration induced significant decrease of small motor movements, atrophy in type IIB muscle fibers and decrease of P-Akt, P-GSK3omega and P-FOXO3a/total FOXO3a expression. Omega-3 supplementation was not able to attenuate these changes. Instead, omega-3 associated to dexamethasone (DX+ omega-3 group) additionally induced higher muscle atrophy in type I, IIA muscle fibers, and reduced expression of Myogenin. The isolated use of Omega-3 led to a significant higher expression of Myostatin and MyoD, and a non-significant increase of total mTOR protein expression and less body weight gain at end of study. Conclusion: Supplementation of omega-3 was not able to attenuate motor behavioral changes, muscle atrophy and loss of body weight caused by dexamethasone administration, leading on the other hand to higher muscle fibers atrophy and increase in atrogenes expression. Therefore, this study suggests that food supplements, usually considered benefic to the health, such as Omega-3 fatty acid, may interact with some medications, such as glucocorticoids, potentiating its side effects (AU)

FAPESP's process: 11/03862-8 - Effects of Omega-3 fatty acid supplementation on prevention of the Dexamethasone-induced muscle atrophy
Grantee:Alan Fappi
Support Opportunities: Scholarships in Brazil - Master