Endoplasmic Reticulum Stress and Autophagy Markers in Soleus Muscle Disuse-Induced Atrophy of Rats Treated with Fish Oil.

Gabriel Nasri Marzuca-Nassr,Kaio Fernando Vitzel,Gilson Masahiro Murata,Rosângela Pavan Torres,Jorge Mancini-Filho,Tatiana Carolina Alba-Loureiro,Rui Curi,Wilson Mitsuo Tatagiba Kuwabara

doi:10.3390/nu13072298

Abstract

Endoplasmic reticulum stress (ERS) and autophagy pathways are implicated in disuse muscle atrophy. The effects of high eicosapentaenoic (EPA) or high docosahexaenoic (DHA) fish oils on soleus muscle ERS and autophagy markers were investigated in a rat hindlimb suspension (HS) atrophy model. Adult Wistar male rats received daily by gavage supplementation (0.3 mL per 100 g b.w.) of mineral oil or high EPA or high DHA fish oils (FOs) for two weeks. Afterward, the rats were subjected to HS and the respective treatments concomitantly for an additional two-week period. After four weeks, we evaluated ERS and autophagy markers in the soleus muscle. Results were analyzed using two-way analysis of variance (ANOVA) and Bonferroni post hoc test. Gastrocnemius muscle ω-6/ω-3 fatty acids (FAs) ratio was decreased by both FOs indicating the tissue incorporation of omega-3 fatty acids. HS altered (p < 0.05) the protein content (decreasing total p38 and BiP and increasing p-JNK2/total JNK2 ratio, and caspase 3) and gene expressions (decreasing BiP and increasing IRE1 and PERK) of ERS and autophagy (decreasing Beclin and increasing LC3 and ATG14) markers in soleus. Both FOs attenuated (p < 0.05) the increase in PERK and ATG14 expressions induced by HS. Thus, both FOs could potentially attenuate ERS and autophagy in skeletal muscles undergoing atrophy.

Highlights

Reductions of ω-6 fatty acids (FAs) (MO: 28%; EPA: 14%; DHA: 7%) and ω-3 FAs (MO: 32%; EPA: 3%; DHA: 4%) observed in the hindlimb suspension (HS) groups were less pronounced in rats treated with fish oils (FOs)
FAs FAs ratios werewere lowered by the
In addition to the above, ω-6/ω-3 ratios lowered by supplementation the supplementation supplementation effect, p oil supplementation effect, p < 0.001) (Supplemental Table S1 and Supplemental Figure S3)

Summary

Introduction

Catabolic states (e.g., cancer and sepsis), and lack of mechanical load cause skeletal muscle atrophy. There are several strategies to treat skeletal muscle atrophy [1,2,3,4]. One of them is dietary supplementation [5,6], including administration of fish oils (FOs) [7]. FOs contain high amounts of eicosapentaenoic (EPA) and docosahexaenoic (DHA), ω-3 fatty acids (FAs). Previous studies reported that these FAs improve conditions with marked skeletal muscle mass loss [8,9,10]. Administration of ω-3 FAs increases protein synthesis [11,12,13] and decreases protein degradation signaling [14,15] in the skeletal muscle

Methods

Results

Conclusion