Effects of high EPA and high DHA fish oils on changes in signaling associated with protein metabolism induced by hindlimb suspension in rats.

Gabriel Nasri Marzuca-Nassr,Rosângela Pavan Torres,Jorge Mancini-Filho,Philip Newsholme,Carlos Flores Rodrigues Junior,Gilson M Murata,Rui Curi,Luís Gustavo De Sousa,Kaio Fernando Vitzel,Amanda Rabello Crisma,Sandro M Hirabara,Phablo Abreu

doi:10.14814/phy2.12958

Gabriel Nasri Marzuca-Nassr, Rosângela Pavan Torres + Show 10 more

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https://doi.org/10.14814/phy2.12958

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Abstract

The effects of either eicosapentaenoic (EPA)‐ or docosahexaenoic (DHA)‐rich fish oils on hindlimb suspension (HS)‐induced muscle disuse atrophy were compared. Daily oral supplementations (0.3 mL/100 g b.w.) with mineral oil (MO) or high EPA or high DHA fish oils were performed in adult rats. After 2 weeks, the animals were subjected to HS for further 2 weeks. The treatments were maintained alongside HS. At the end of 4 weeks, we evaluated: body weight gain, muscle mass and fat depots, composition of fatty acids, cross‐sectional areas (CSA) of the soleus muscle and soleus muscle fibers, activities of cathepsin L and 26S proteasome, and content of carbonylated proteins in the soleus muscle. Signaling pathway activities associated with protein synthesis (Akt, p70S6K, S6, 4EBP1, and GSK3‐beta) and protein degradation (atrogin‐1/MAFbx, and MuRF1) were evaluated. HS decreased muscle mass, CSA of soleus muscle and soleus muscle fibers, and altered signaling associated with protein synthesis (decreased) and protein degradation (increased). The treatment with either fish oil decreased the ratio of omega‐6/omega‐3 fatty acids and changed protein synthesis‐associated signaling. EPA‐rich fish oil attenuated the changes induced by HS on 26S proteasome activity, CSA of soleus muscle fibers, and levels of p‐Akt, total p70S6K, p‐p70S6K/total p70S6K, p‐4EBP1, p‐GSK3‐beta, p‐ERK2, and total ERK 1/2 proteins. DHA‐rich fish oil attenuated the changes induced by HS on p‐4EBP1 and total ERK1 levels. The effects of EPA‐rich fish oil on protein synthesis signaling were more pronounced. Both EPA‐ and DHA‐rich fish oils did not impact skeletal muscle mass loss induced by non‐inflammatory HS.

Highlights

Skeletal muscle mass loss occurs in response to disuse, aging, starvation, and severe catabolic states
We investigated the effects of either eicosapentaenoic (EPA)-rich or docosahexaenoic (DHA)-rich fish oil on signaling pathways associated with protein synthesis and degradation in an experimental condition of intense skeletal muscle mass loss
We examined and compared the effects of EPA- and DHA-rich fish oils on signaling pathways associated with protein synthesis and degradation in a condition of intense skeletal muscle mass loss induced by hindlimb suspension, a model of skeletal muscle disuse as occurs in bed rest or spaceflight conditions in humans

Summary

Introduction

Skeletal muscle mass loss occurs in response to disuse (e.g., immobilization, denervation or lack of mechanical load), aging (sarcopenia), starvation, and severe catabolic states (such as cancer cachexia and sepsis). Muscle atrophy is associated with a decrease in activity of protein synthesis and/or an increase in protein degradation signaling These two pathways are highly regulated via growth factor effects and are interrelated (Jackman and Kandarian 2004). Fish oil has been postulated, in review articles, as a potential attenuating agent of skeletal muscle atrophy (Magne et al 2013; Wall and van Loon 2013; D’Antona et al 2014). We investigated the effects of either eicosapentaenoic (EPA)-rich or docosahexaenoic (DHA)-rich fish oil on signaling pathways associated with protein synthesis and degradation in an experimental condition of intense skeletal muscle mass loss

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