Effects of malnutrition with or without eicosapentaenoic acid on proteolytic pathways in diaphragm

Attenuation of muscle wasting has been reported with eicosapentaenoic acid (EPA) use in cachectic states. Pathways mediating muscle proteolysis with severe short-term nutritional deprivation (ND) ± EPA were evaluated, including diaphragm fiber-specific cross-sectional areas, mRNA (real-time PCR) and protein expression (Western blot). Rats were divided into three groups: (1) free-eating controls, (2) ND and (3) ND + EPA. ND significantly influenced multiple proteolytic pathways. EPA significantly reduced mRNA abundances for most genes to control levels with ND. However, discordant muscle protein expression of many genes was noted with the use of EPA, as protein levels failed to fall. EPA had no impact on diaphragm muscle atrophy, despite the impressive mRNA and some protein results. We conclude that EPA does not attenuate diaphragm muscle atrophy with severe levels of ND. Postulated mechanisms include reduction in muscle protein synthesis and persistent ongoing stimuli for proteolysis. Our study provides unique data on proteolytic signals with ND and has important implications for future studies using EPA.

► Proteolytic pathways were studied in the malnourished (ND) diaphragm ± EPA treatment.
► EPA significantly reduced mRNA abundances for most genes to control levels with ND.
► Muscle protein levels failed to fall with the use of EPA despite robust mRNA changes.
► EPA had no impact on individual diaphragm muscle fiber atrophy.
► Reduced protein synthesis and persistent proteolytic stimuli are likely explanations.